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Meds, Mind, Body & Benefits => Research News & Studies => Topic started by: veritas on July 19, 2008, 11:02:59 am

Title: Could this be the holy grail ?
Post by: veritas on July 19, 2008, 11:02:59 am
http://www.wipo.int/pctdb/en/wads.jsp?IA=US2007024122&LANGUAGE=EN&ID=id00000006427540&VOL=87&DOC=0084d3&WO=08/063586&WEEK=22/2008&TYPE=A2&DOC_TYPE=PAMPH&PAGE=1
Title: Re: Could this be the holy grail ?
Post by: Ann on July 19, 2008, 11:27:23 am
Veritas, your link does not work.
Title: Re: Could this be the holy grail ?
Post by: veritas on July 19, 2008, 11:45:53 am
ANN,
I just tried it again and it worked for me. All I did was single click on the link. In short the link takes you to apatent application by the researches at DUKE university. DUKE is where the headquarters of CHAVI (commitee of hiv and aids vaccine initiative) is located. CHAVI is aglobal initiative in conjunction with CAVD,IAVI and more than 40 researches and 9 institutions backed by the patronage of Bill and Melinda Gates foundation to find a cure and a vaccine. The patent is 97 pages of wonderful !! Please try again and I'lll try to find another link.
Title: Re: Could this be the holy grail ?
Post by: veritas on July 19, 2008, 11:50:22 am
Try this one it is another patent from the same group:

     http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&u=%2Fnetahtml%2FPTO%2Fsearch-adv.html&r=2&p=1&f=G&l=50&d=PG01&S1=%28%22haynes+Barton%22.IN.%29&OS=in/%22haynes+Barton%22&RS=IN/%22haynes+Barton
Title: Re: Could this be the holy grail ?
Post by: Ann on July 19, 2008, 02:01:24 pm
Your first link still doesn't work for me. I just get a screen saying "image loading" but ten minutes later it was still "loading". I'm on broadband, so it's not a slow connection problem.

Title: Re: Could this be the holy grail ?
Post by: Miss Philicia on July 19, 2008, 02:06:18 pm
Actually it works for me, but it's a .pdf file so your browser must either be configured to view this in line or you have to download it to your drive and open it up in Acrobat.

I'll try linking it a better way:

link (http://www.wipo.int/pctdb/en/wads.jsp?IA=US2007024122&LANGUAGE=EN&ID=id00000006427540&VOL=87&DOC=0084d3&WO=08/063586&WEEK=22/2008&TYPE=A2&DOC_TYPE=PAMPH&PAGE=1)

(I'm still wary of "holy grail" claims, and it seems we're having one every day in the Research News section of the forums...)
Title: Re: Could this be the holy grail ?
Post by: veritas on July 19, 2008, 02:23:37 pm
Philly.

If the link worked for you, go to the top of the right side of the page and you will see a box that says  pdf page by page. Click on the down arrow that shows pdf 97 pages. Click on 97 pages and it should come up for you. Let me know.
Title: Re: Could this be the holy grail ?
Post by: Miss Philicia on July 19, 2008, 02:25:46 pm
Uh, honey -- I just said I got it to work.  I'm well aware of how to manipulate a .pdf file in a portable document reader application. 

I have no interest in reading 97 pages of a .pdf file, but thanks.  I'll leave that to someone else here to do.

Not trying to be rude or anything, but I'm afraid I just don't have the time right now.

By the way, welcome to the forums.
Title: Re: Could this be the holy grail ?
Post by: veritas on July 20, 2008, 09:08:09 am
Philly,

Your response to me made me realise that the patent is not an easy read without the background research needed to understand the method of action of this new paradigm. Reading a pdf file can be daunting and I thankyou for pointing this out. Let me try to paraphrase the invention and if there are any science-types out there who have read the patent and understand the moa, I welcome any corrections.

Let me preface my statements by saying that I am not a scientist, professional researcher or doctor. I, like many of you, am tired of taking toxic drugs with all the accompanying sides, however, I am certainly thankful for the job that these drugs have done to extend life. My intention here is not to open my own bag of woe, but to show that research is proceeding at an amazing rate and that I believe a breakthrough is closer than we think.

This patent is based on anti-phosphilipid therapy (anti-ps). Phosphilipids are present in every cell in the human body, however, they are usually pointed inward to the cell providing among other things,nourishment to the cell. When a cell is about to die (apoptosis) these phosphilipids turn outward and eventually the dead cells are removed. The immune system recognizes this as a normal process and leaves these cells alone until they are dead. When a virus (like HIV) enters a cell this same phosphipid flip occurs however the cell does not die immediately tricking the immune system into thinking this a natural occurring process. Also these phosphlipids are providing nourisment to the virus. When the virus breaks out, it takes along some of these phosphilipids for its own use and they are also pointing outward on the virus protecting the virus from the immune system. Dr. Haynes et al. have found that certain broadly neutralising antibodies (ie:4e10,2f5,is1 among others) are able to recognize this deception by the virus and go in for the kill. These antibodies are also able to go after those cells infected with the virus leaving normal apoptosis alone.

The work is brilliant and elegant and many components have already been tested both preclinically and clinically. I refer you to the chavi.org to view the clinical trials comprising some of the components that have been tested. For those of you that are so inclined, you can look up the reseach of the principal investigators on pub med. It's adaunting task!

My explanation herein is certainly elementary but I have tried to give all as simple an explanation as I can. Again, if anyone can see any errors or corrections please don't hesitate to correct me. By the way, the vaccine teaches your immune system to do the job on its own.
Please forgive me for the long post.

veritas
Title: Re: Could this be the holy grail ?
Post by: veritas on September 25, 2008, 04:56:02 am
Further research on anti-ps to be presented in Oct Aids conference.


OA03-06
Anti-lipid Human Monoclonal Antibodies Inhibit HIV-1 Infection
of PBMC by Binding to Host Cells
MA Moody1, MK Plonk1, L Fuller1, H Liao1, S Xia1, MS Drinker
1, TC Gurley1, RMScearce1, GD Tomaras1, C Chang2, S King2,
A Kavlie3, PE Thorpe4, SM Alam1, PP Chen5, DC Montefiori6,
and BF Haynes1

1Duke University Medical Center, Durham, NC, USA; 2Peregrine
Pharmaceuticals, Tustin, CA, USA; 3Affitech AS, Oslo, N-0349,
Norway; 4University of Texas Southwestern Medical Center,
Dallas, TX, USA; 5UCLA School of Medicine, Los Angeles, CA,
USA; 6Department of Surgery, Duke University Medical Center,
Durham, NC, USA

Background: HIV-1-infected or vaccinated humans rarely make
broadly-reactive neutralizing antibodies. Some antibodies against
conserved Env epitopes share similarities with autoantibodies; one
hypothesis is such antibodies are downregulated by immune tolerance.
The observation that AIDS may be rare in primary autoimmune
disease patients (1) prompted the hypothesis that autoimmune
disease patients with defective tolerance mechanisms may make
antibodies that in some manner protect against HIV-1 infection.
Methods: We studied a panel of human anti-lipid mAbs from
autoimmune disease patients and healthy controls. Mabs IS4, CL1,
P1, and PGN632 bind cardiolipin and phosphatidylserine independent
of b2-glycoprotein I; mAbs B1, B2, PGN634, and
PGN635 require b2-glycoprotein I for lipid binding. Inhibition of
HIV-1 infection was studied using HIV-1 Env pseudoviruses in
TZM/bl cells and using whole virus assays in peripheral blood
mononuclear cells (PBMC). MAb interaction with Env, lipids, and
cells was determined by surface plasmon resonance (SPR), flow
cytometry, and fluorescent microscopy.
Results: No mAbs bound HIV-1 wild-type Envs by SPR and none
significantly neutralized HIV-1 primary isolate pseudoviruses in
the TZM/bl assay. In PBMC, b2-glycoprotein I-dependent mAbs
minimally inhibited infection. In contrast, b2-glycoprotein
I-independent anti-lipid mAbs (PGN632, P1, IS4, CL1) inhibited
HIV-1 primary isolate infection of PBMC (IC80s<0.02 to 45 mg/
mL). The most potent mAb PGN632 inhibited 7/7 B and C clade
HIV-1 isolates (IC80s<0.02-0.16 mg/mL) and SHIV SP162P3
(IC80 0.06 mg/mL). Cell preincubation and virus capture studies
showed the mAbs acted at host cell surfaces to inhibit HIV-1 infection.
Immunofluorescence of CD4þ T cells showed the mAbs
bound to lipid rafts.
Conclusion: Anti-lipid human mAbs inhibit HIV-1 infection in
vitro in PBMC likely by binding CD4þ T cell lipid rafts. Testing
these mAbs in passive therapy trials in vivo in non-human primates
will be important to determine their protective effect. Nonpathogenic
anti-lipid antibodies may provide a target for HIV-1
vaccine development.



 
Title: Re: Could this be the holy grail ?
Post by: newt on September 25, 2008, 04:47:28 pm
This is promising. I kinda feel smug cos I pointed out this line of research in 2003 to Most Eminent Researchers who were frankly patronising on the idea that it may be important.

Holy grail ... I will break out my deckchair and the Scotch (as usual) and wait for the Phase I-III human studies

Being a monoclonal antibody it is fraught with the usual genetics/haplotype hazards (so long time in the sun drinkiing, note to self: not good for health)

- matt
Title: Re: Could this be the holy grail ?
Post by: veritas on September 26, 2008, 04:41:14 am

Anti-ps is already in clinical trials.

 http://clinicaltrials.gov/ct2/show/NCT00503347?term=bavituximab&rank=4
Title: Re: Could this be the holy grail ?
Post by: leit on September 26, 2008, 04:10:02 pm

In your opinion, are phosphatidylserine supplements (http://www.super-smart.eu/en--Neuro-nutrition--PS-100--0075) or even only PS-containing foods (http://en.wikipedia.org/wiki/Phosphatidylserine#Dietary_Sources) dangerous for us?
Thank you!

Title: Re: Could this be the holy grail ?
Post by: veritas on September 27, 2008, 03:54:06 am
leit,
I have not done any research on PS supplements
Title: Re: Could this be the holy grail ?
Post by: veritas on October 01, 2008, 10:00:36 am

http://www.cavd.org/grantees/pages/progressAbstracts_Haynes.aspx
Project: Broadly Reactive Neutralizing Antibodies: Novel Strategies for Vaccine Design
 

Submitted September 22, 2008
Our goal is to acquire proof of concept data that manipulation of the immunoregulatory controls of B cell immune responses to HIV-1 Env, coupled with enhanced immunogen design, can lead to safe induction of broadly reactive neutralizing antibody responses. We are using a two armed approach to the problem of induction of antibodies that broadly neutralize HIV.

The Kelsoe, Haynes and Thorpe laboratories are developing immunogen formulations that trigger B cells normally tolerant to the desired Envelope epitopes and regions. Garnett Kelsoe is determining the origins, development, physiology, and fates of marginal zone, transitional and B1 B cell populations in animal models including mice and non-human primates. Haynes is determining the role of tolerance mechanisms, and TLR signaling on control of broadly reactive B cell activation, and Philip Thorpe is determining the role of lipid binding of anti-HIV antibodies and anti-phosphatidylserine (PS) autoantibodies to protection from HIV infection. We have completed the first protection trial to determine if anti-beta-2-glycoprotein-1 antibodies can prevent infection or early viral destruction of the immune system in acute SIV infection and these pathogenic anti-lipid antibodies do not prevent HIV-1 and SIV infection in vitro and do not protect against SIV-1 infection in vivo. The team has recently found that non-pathogenic anti-lipid antibodies that do not require beta-2-glycoprotein-1 for lipid binding do prevent HIV-1 and SHIVSF162P3 (and all R5 HIVs tested from infecting PBMC in vitro, and a prototype of non-pathogenic anti-lipid antibodies will be studied in vivo for the ability to protect against R5 SHIV infection.

The Harrison, Alam, Spicer, Shaw, Robinson and Hahn laboratories are developing immunogens that are in native conformations and are being tested for induction of neutralizing antibodies. These include HIV Env immunogens with a spectrum of affinities for binding to broadly reactive neutralizing antibodies, and immunogens with low entropic barriers to Mab binding and therefore are thermodynamically stable. Steve Harrison, Bing Chen and Larry Liao have made single chain Fv 4E10 antibodies and whole IgG1 2F5 Mabs with mutations that selectively eliminate gp41 or lipid reactivity. They have demonstrated that both 2F5 and 4E10 require the capacity to bind to lipids to neutralize HIV-1. They will now use the Fvs and Mabs in co-crystallization efforts with trimeric gp120/gp41 constructs. Munir Alam has designed gp41 peptide lipid conjugates using 4E10 and 2F5 epitopes peptides. He is characterizing the binding kinetics, and thermodynamic properties of 4E10 and 2F5 binding to peptide-lipid conjugates. Heather Desaire is characterizing the carbohydrates of HIV-1 Env produced in T cells and macrophages, and Haynes is determining methods for making these “autoantigens” immunogenic. Spicer is studying the lipid-peptide conjugates for their structures by NMR. George Shaw and Beatrice Hahn have constructed HIV-1/HIV-2 chimeras with HIV-2 neutralizing determinants in HIV-1 scaffolds, to study the neutralization of HIV-2 with James Robinson . The Team led by Victor Chalwe at the Tropical Disease Research Laboratory in Ndola, Zambia is providing the CAVD with PBMC and plasma on a series of chronically infected subjects for mapping epitopes of broadly neutralizing antibodies for immunogen design.

 

Title: Re: Could this be the holy grail ?
Post by: veritas on October 03, 2008, 10:22:52 am

A lot of research is being done with antibodies for HIV and other indications.


http://www.the-infoshop.com/conference/antibodyeng08/atagenda.shtml
Title: Re: Could this be the holy grail ?
Post by: leit on October 03, 2008, 03:52:24 pm
A lot of research is being done with antibodies for HIV and other indications.
http://www.the-infoshop.com/conference/antibodyeng08/atagenda.shtml

Ok, let's talk about these WONDER-DRUGS. Panitumumab ("Vectibix") (http://www.farmamondo.com/vista.cfm?ID=1960&LI=E), for instance, a monoclonal antibody "for the treatment of patients with colorectal cancer that has metastasized following standard chemotherapy".

DOSES

"The recommended dose of Vectibix is 6mg/kg administered [...] every 14 days".
So, if one person weights even only 70 Kg, the dose becomese 6*70 = 420 mg every 14 days. Since 20 mg of "Vectibix" cost 5,175.83 $, the "therapy" costs 5,175.83*420/20/14 = 7,763.745 $ A DAY.

RESULTS

"The mean time to disease progression or death in patients receiving Vectibix was 96 days versus 60 days in patients receiving the best standard supportive care. [...] Both study groups showed similar overall survival."
(Let alone dermatological side effects)

BOTTOM LINE

One pays 36 DAYS OF POSSIBLE EXTRA-AGONY 7,763.745 $ EACH.

_THIS_IS_SHIT_ (and I wonder how could the FDA approve it).

Title: Re: Could this be the holy grail ?
Post by: bimazek on October 03, 2008, 05:34:32 pm
that is silly to say that a monoclonal antibody for cancer is worthless -- a monoclonal antibody is like a wrench or a screw driver it is a tool to heal the body, the mechanic needs lots of tools and development of a new tool is a good thing

 science is still in its infancy in the use of monoclonal antibodies for cancer, some day there may be a triple cocktail of monoclonal antibodies for a specific cancer with 99% cure rate like the HIV HAART triple cocktail

you are taking one tiny step in science and trying to burn at the stake all science progress,

it is like man learning how to fly -- man saw the wings of birds for thousands of years and dreamed and then slowly they figured out the Wright brothers wing then it took millions of men working to innovate the metal airplane and the jet engine etc.

as i have said before, the immune system is a complex system, it is more than the SUM of its parts

http://en.wikipedia.org/wiki/Complex_system

it is also NOT a closely coupled system, the body, if it were if you stubbed your toe it would cause a heart attack
closely coupled system
http://poderigiacomo.netsons.org/blog/archives/90

these are extremely complex ideas to even understand

cancer -- and this was discovered a few weeks ago is not simple like HIV -- science had hoped that it was a few genes that went wrong in same way, the new discovery is cancer is

thousands of genes going wrong in millions of ways so there are trillions of different kinds of cancer -- anotehr way to look at it is everyone has thier own unique cancer based on thier own unique genes

this is a simplification







Title: Re: Could this be the holy grail ?
Post by: leit on October 03, 2008, 09:25:20 pm
that is silly to say that a monoclonal antibody for cancer is worthless -- a monoclonal antibody is like a wrench or a screw driver it is a tool to heal the body, the mechanic needs lots of tools and development of a new tool is a good thing

Well, when the mechanic has ALL the necessary tools, he will start his workshop. Until then, he CANNOT ask to be paid 7,763.745$ a day for his badly made jobs.

Title: Re: Could this be the holy grail ?
Post by: veritas on October 04, 2008, 05:24:51 am

Leit and bimazek,

Both of you have some very good points. The cost of some of these medications are outrageous with a somewhat less than satisfactory side affect profile and not much life extension. But as bimazek points out you have to start somewhere.

This is why I am hopeful about anti-ps. In the phase 1 clinical trials for Bavituximab for cancer and Hep C the mab had top line safety data and some efficacy(phase 1). Cancer cells also flip phosphilipids. Hiv iis a retrovirus like Hep C so the mab should do the same for Hiv. I anxiously await the interim data from the co-infection trial of Hep C and HIV with Bavituximab. I posted this clinical trial in an earlier reply.

veritas
Title: Re: Could this be the holy grail ?
Post by: veritas on October 04, 2008, 09:25:12 am
More anti-ps research found:








HIV - Phosphatidylserine Breakthrough









The July announcement by NIAID Director Dr. Anthony Fauci to scrap the upcoming "PAVE-100" HIV vaccine clinical trial, (following on the heels of the failed Merck "STEP" HIV vaccine trial), showed yet again how difficult and elusive the goal of an effective HIV vaccine remains.

In the midst of these sobering developments, an important new insight was gained into why experimental HIV vaccines have failed to elicit an adequate immune response. The discovery, published in the August issue of the Journal of Virology (1), came from the leader of NIAID's “CHAVI” organization, Dr. Barton Haynes of Duke University, who is also a principle investigator of the Gates Foundation HIV vaccine effort.

In their paper, Haynes and colleagues discuss experiments showing that HIV weakens the immune system much faster than previously thought. The primary mechanism responsible for this immunosuppression is an overwhelming amount of what Haynes terms "microparticles", which are tiny particles shed from the outer membranes of infected and dying cells. This cellular debris accumulates during early HIV infection, and circulates throughout the body blunting the functions of the immune cells that would ideally fight the virus. Popular news articles have discussed this aspect of the Duke researchers' findings, but the details and broader implications of the team's discovery have yet to be elucidated in the media.

The paper explains that the microparticles contain the molecule phosphatidylserine (PS) exposed on their surface. PS is a lipid that normally lines the interior of the cell membranes of every cell in our body. As a cell dies, it loses the ability to maintain PS on the inside of the cell membrane. The PS flips to the exterior, where it is perceived by immune cells as a sign of a dying native cell. The Haynes team cite recent data showing how exposed PS appears to be the fundamental signal that shifts the behavior of immune cells into not mounting an antigen-specific attack, since PS is interpreted as a sign of “self” rather than a foreign invader (2). Other researchers have also recently illustrated the suppressive effects of PS on macrophages, the resulting cytokine environment, dendritic cells, and T cells (3-7). It is thus no surprise that recent research has also revealed exposed PS as a feature common to many diverse pathogens (8-22), as if they independently evolved to exploit a similar mechanism of evasion, since it provides the crucial advantage of triggering an inappropriate immune response, facilitating the pathogen's survival and proliferation.

A review of Haynes' recent patent applications provides further details that have yet to be published in the journals. In one application, titled “Multicomponent Vaccine” (23), Haynes explains that any future successful HIV vaccine must interrupt this PS-mediated immunosuppressive signaling. A specific goal mentioned is for a vaccine to induce antibodies to PS (anti-PS), thereby blocking the overwhelming immune suppression seen in the Duke research, allowing the viral immunogen in the vaccine the chance to evoke T and B cells which effectively fight the virus.

In yet another recent patent application, Haynes proposes using anti-PS as a promising treatment for people already infected with the virus (24). He discusses the ability of anti-PS monoclonal antibodies to bind to HIV and HIV-infected cells, saying anti-PS "can be safely used as a therapeutic Mab for treatment of HIV infected subjects", and that it can "broadly neutralize HIV in an unprecedented manner".


Perhaps the most fascinating comment found in one of Haynes' many recent patent applications is his suggestion that HIV's method of immune evasion may be a general escape mechanism utilized by other pathogens (24), and that similar means of therapy may be effective against other diseases. Indeed, a review of the recent major journals corroborates this concept:

In April, the journal Science published experiments showing that the pox family of viruses, (vaccinia), utilize exposed PS to gain entry into cells (25).

In the March issue of the journal Clinical Cancer Research, scientists from Harvard University discuss experiments in which blocking PS signaling helped facilitate complete melanoma tumor regressions (26).

The protozoan parasites responsible for many of the deadly diseases affecting much of the developing world have been found to rely on exposed PS to successfully avoid the immune system of their host (16-22).

Several cancer researchers have recently published data which bears a striking resemblance to the new findings of the Haynes HIV group, showing a very similar method of systemic immune suppression caused by PS-exposing microparticles shed from tumor cells (29-34), (see also 27, 28).

In another recent Haynes patent application he also discusses PS-exposing microparticles as playing a role in the pathogenesis of several auto-immune diseases as well as atherosclerosis (35), (see also 36-40).




Taken together, these discoveries suggest a new immunological perspective of pathogenesis in general. A paradigm appears to be emerging in which the necessary and admirable flexibility of the immune system has been exploited precisely where it is most vulnerable – when it must commit to a 'friendly' response. The recent HIV research by Haynes and colleagues, focusing on PS-induced immune suppression, and the safe therapeutic targeting of exposed PS with antibodies, carries implications of unprecedented broad therapeutic potential.




References:

1. Nancy Gasper-Smith, Deanna M. Crossman, John F. Whitesides, Nadia Mensali, Janet S. Ottinger, Steven G. Plonk, M. Anthony Moody, Guido Ferrari, Kent J. Weinhold, Sara E. Miller, Charles F. Reich III, Li Qin, Stephen G. Self, George M. Shaw, Thomas N. Denny, Laura E. Jones, David S. Pisetsky, and Barton F. Haynes, 2008, Induction of Plasma (TRAIL), TNFR-2, Fas Ligand, and Plasma Microparticles after Human Immunodeficiency Virus Type 1 (HIV-1) Transmission: Implications for HIV-1 Vaccine Design, The Journal of Virology, Vol. 82, No. 15




2. Peter R. Hoffmann, Jennifer A. Kench, Andrea Vondracek, Ellen Kruk, David L. Daleke, Michael Jordan, Philippa Marrack, Peter M. Henson and Valerie A. Fadok, 2005, Interaction between Phosphatidylserine and the Phosphatidylserine Receptor Inhibits Immune Responses In Vivo. The Journal of Immunology, 174: 1393-1404.




3. Lars-Peter Erwig and Peter M. Henson, 2007, Immunological Consequences of Apoptotic Cell Phagocytosis Am J Pathol. July; 171(1): 2–8.




4. Xiao Chen, Kara Doffek, Sonia L. Sugg and Joel Shilyansky , 2004. Phosphatidylserine Regulates the Maturation of Human Dendritic Cells The Journal of Immunology, 173: 2985-2994.




5. Celio G. Freire-de-Lima∗, Yi Qun Xiao, Shyra J. Gardai, Donna L. Bratton, William P. Schiemann, and Peter M. Henson, 2006, Apoptotic cells, through transforming growth factor-beta, coordinately induce anti-inflammatory and suppress pro-inflammatory eicosanoid and NOsynthesis in murine macrophages. J. Biol. Chem., Vol. 281, Issue 50, 38376-38384




6. Satoshi Yotsumoto, Terutaka Kakiuchi and Yukihiko Aramaki, 2005, Negatively charged phospholipids suppress IFN-gamma production in T cells. Biochemical and Biophysical Research Communications, Volume 338, Issue 4,




7. Dongmei Shi, Meng Fu, Pinshen Fan, Wei Li, Xinhui Chen, Chenxin Li, Xianlong Qi, Tianwen Gao and Yufeng Liu, 2007, Artificial phosphatidylserine liposome mimics apoptotic cells in inhibiting maturation and immunostimulatory function of murinemyeloid dendritic cells in response to 1-chloro-2,4-dinitrobenze in vitro . Archives of Dermatological Research Volume 299, Number 7




8. Ryungsa Kim, Manabu Emi, Kazuaki Tanabe, 2005. Cancer Cell Immune Escape and Tumor Progression by Exploitation of Anti-Inflammatory and Pro-Inflammatory Responses. Cancer Biology & Therapy 4:9, 924-933




9. Ryungsa Kim, Manabu Emi, Kazuaki Tanabe and Koji Arihiro, 2006, Tumor-Driven Evolution of Immunosuppressive Networks During Malignant Progression. Cancer Research 66, 5527-5536




10. Melissa K. Callahan, Paul M. Popernack, Shigeki Tsutsui, Linh Truong, Robert A. Schlegel, and Andrew J. Henderson, 2003. Phosphatidylserine on HIV Envelope Is a Cofactor for Infection of Monocytic Cells The Journal of Immunology, 170: 4840-4845




11. David A. Coil and A. Dusty Miller, 2005. Enhancement of Enveloped Virus Entry by Phosphatidylserine Journal of Virology, p. 11496-11500, Vol. 79, No. 17.




12. Shawn J. Green, 2006. Could a vaccine to cholesterol cause a wrinkle in the HIV-1 envelope? Public Library of Science Journal of Biology, Published: November 22, 2006




13. David A. Coil and A. Dusty Miller, 2005. Phosphatidylserine treatment relieves the block to retrovirus infection of cells expressing glycosylated virus receptors Retrovirology 2005, 2:49




14. Ge Ma, Teresa Greenwell-Wild, Kejian Lei, Wenwen Jin, Jennifer Swisher, Neil Hardegen, Carl T. Wild, and Sharon M. Wahl, Secretory Leukocyte Protease Inhibitor Binds to Annexin II, a Cofactor for Macrophage HIV-1 InfectionJEM, Volume 200, Number 10, 1337-1346




15. N Gasper-Smith, JF Whitesides, N Mensali, JS Ottinger, SG Plonk, MA Moody, G Ferrari, KJ Weinhold, CF Reich, DS Pisetsky and BF Haynes, 2007, Plasma FAS ligand, TNFR2, and TRAIL levels are elevated during the time of viral load ramp-up in acute HIV-1 infection AIDS Vaccine 2007 Conference, Seattle Washington, August 20-23, 2007, PO1-01.




16. Shigetoshi Eda, Irwin Sherman, 2002, Cytoadherence of Malaria-Infected Red Blood Cells Involves Exposure of Phosphatidylserine Cell Physiol Biochem 12:373-384




17. Sergio H. Seabra, Wanderley de Souza and Renato A. DaMatta, 2004, Toxoplasma gondii exposes phosphatidylserine inducing a TGF-beta1 autocrine effect orchestrating macrophage evasion. Biochemical and Biophysical Research Communications, Volume 324, Issue 2, pages 744-752.




18. Desiree van der Kleij, Eicke Latz, Jos F. H. M. Brouwers, Yvonne C. M. Kruize, Marion Schmitz, Evelyn A. Kurt-Jones, Terje Espevik, Esther C. de Jong, Martien L. Kapsenberg, Douglas T. Golenbock, Aloysius G. M. Tielens, and Maria Yazdanbakhsh, 2002. A Novel Host-Parasite Lipid-Crosstalk J. Biol. Chem., Vol. 277, Issue 50, 48122-48129




19. Renato A. DaMatta , Sergio H. Seabra, Poliana Deolindo, Andréa C. V. Arnholdt, Lauro Manhães, Samuel Goldenberg, Wanderley de Souza, 2007. Trypanosoma cruzi exposes phosphatidylserine as an evasion mechanism FEMS Microbiology Letters,Volume 266 Issue 1 Page 29-33




20. Annalena Bollinger, 2005, Leishmania Major Promastigotes Use Phosphatidylserine For Silencing Of Polymorphonuclear Neutrophils Doctoral dissertation in partial fulfillment of the requirements for the degree of Doctor of Natural Sciences (Dr. rer. nat.) from the University of Lübeck - Faculty of Technology and Sciences




21. J.L.M. Wanderley, A. Benjamin, F. Real, A. Bonomo, M.E.C. Moreira and M.A. Barcinski, 2005, Apoptotic mimicry: an altruistic behavior in host/Leishmania interplay Braz J Med Biol Res, June 2005, Volume 38(06) 807-812




22. José Mario de Freitas Balanco, Maria Elisabete Costa Moreira, Adriana Bonomo, Patricia Torres Bozza, Gustavo Amarante-Mendes, Claude Pirmez and Marcello André Barcinski, 2001, Apoptotic mimicry by an obligate intracellular parasite downregulates macrophage microbicidal activity Current Biology, Volume 11, Issue 23, Pages 1870-1873




23 HAYNES, Barton, F., SMITH, Nancy, G., ALAM, S., Munir GAO, Feng LIAO, Hua-Xin, Publication Date:29.05.2008, (WO/2008/063586) MULTICOMPONENT VACCINE, World Intellectual Property Organization patent application WO/2008/063586




24. Haynes; Barton F., published March 6, 2008, Method of inducing neutralizing antibodies to human immunodeficiency virus, US patent application 20080057075




25. Jason Mercer, Ari Helenius, 2008. Vaccinia Virus Uses Macropinocytosis and Apoptotic Mimicry to Enter Host Cells

Science, 2008 Apr 25;320(5875):531-5.




26. Catia Fonseca and Glenn Dranoff, 2008. Capitalizing on the Immunogenicity of Dying Tumor Cells Clinical Cancer Research 14, 1603-1608.




27. J. H. W. Distler, L. C. Huber, A. J. Hueber, C. F. Reich III, S. Gay, O. Distler and D. S. Pisetsky, 2005, The release of microparticles by apoptotic cells and their effects on macrophages The Journal of Apoptosis, Volume 10, Number 4, Pages 731-741




28. Lars C. Huber, Astrid Jüngel, Jörg H. W. Distler, Falk Moritz, Renate E. Gay, Beat A. Michel, David S. Pisetsky, Steffen Gay and Oliver Distler, 2006. The role of membrane lipids in the induction of macrophage apoptosis by microparticles The Journal of Apoptosis, Volume 12, Number 2, Pages 363-374




29. Roberta Valenti, Veronica Huber, Manuela Iero, Paola Filipazzi, Giorgio Parmiani and Licia Rivoltini, 2007, Tumor-Released Microvessicles as Vehicles of Immune Suppression. Cancer Research 67, 2912-2915




30. Roberta Valenti, Veronica Huber, Paola Filipazzi, Lorenzo Pilla, Gloria Sovena, Antonello Villa, Alessandro Corbelli, Stefano Fais, Giorgio Parmiani and Licia Rivoltini, 2006, Human Tumor-Released Microvesicles Promote the Differentiation of Myeloid Cells with Transforming Growth Factor-ß–Mediated Suppressive Activity on T Lymphocytes Cancer Research 66, 9290-9298




31. Aled Clayton, J. Paul Mitchell, Jacquelyn Court, Malcolm D. Mason and Zsuzsanna Tabi, 2007, Human tumor-derived exosomes selectively impair lymphocyte responses to interleukin-2 Cancer Research 67, 7458-7466




32. Veronica Huber, Stefano Fais, Manuela Iero, Luana Lugini, Paola Canese, Paola Squarcina, Annamaria Zaccheddu, Marisa Colone, Giuseppe Arancia, Massimo Gentile, Ettore Seregni, Roberta Valenti, Giuseppina Ballabio, Filiberto Belli, Ermanno Leo, Giorgio Parmiani and Licia Rivoltini, 2005, Human colorectal cancer cells induce T-cell death through release of proapoptotic microvesicles: role in immune escape. Gastroenterology, Volume 128, Issue 7, Pages 1796-1804.




33. Shaohua Yu, Cunren Liu, Kaihong Su, Jianhua Wang, Yuelong Liu, Liming Zhang, Chuanyu Li, Yingzi Cong, Robert Kimberly, William E. Grizzle, Carla Falkson and Huang-Ge Zhang, 2007, Tumor exosomes inhibit differentiation of bone marrow dendritic cells. The Journal of Immunology, 178: 6867-6875




34. M Iero, R Valenti, V Huber, P Filipazzi, G Parmiani, S Fais and L Rivoltin, 2008, Tumour-released exosomes and their implications in cancer immunity Cell Death and Differentiation 15, 80–88




35. HAYNES, Barton, F. , SMITH, Nancy, G. , Publication Date:24.07.2008, METHOD OF MONITORING HIV INFECTION World Intellectual Property Organization patent application WO/2008/088747




36. Tedqui, A, Mallat, Z, 2003, Apoptosis, a major determinant of atherothrombosis. Arch Mal Coeur Vaiss, 96(6):671-5




37. Morel O, Toti F, Bakouboula B, Grunebaum L, Freyssinet JM., 2006, Procoagulant microparticles: 'criminal partners' in atherothrombosis and deleterious cellular exchanges Pathophysiology of Haemostasis and Thrombosis, 35(1-2):15-22




38. S. P. Ardoin, J. C. Shanahan, D. S. Pisetsky, 2007 The role of microparticles in inflammation and thrombosis Scandinavian Journal of Immunology 66 (2-3) , 159–165




39. Nikos Werner; Sven Wassmann; Patrick Ahlers; Sonja Kosiol; Georg Nickenig, 2006, Circulating CD31+/annexin V+ apoptotic microparticles correlate with coronary endothelial function in patients with coronary artery disease. Arteriosclerosis, Thrombosis, and Vascular Biology. 26:112


40. Liudmila Zakharova, Maria Svetlova, Alla F. Fomina, 2006. T cell exosomes induce cholesterol accumulation in human monocytes via phosphatidylserine receptor Journal of Cellular Physiology, Volume 212, Issue 1, Pages 174-181.

Title: Re: Could this be the holy grail ?
Post by: veritas on October 10, 2008, 05:22:11 am

Interesting:


http://www.dukehealth.org/HealthLibrary/News/scientists_find_first_immune_responses_to_hiv_infection_ineffective
Title: Re: Could this be the holy grail ?
Post by: leit on October 11, 2008, 01:27:53 pm
Interesting:

Hi, "veritas"!

Your posts are always very interesting. Could you please change their subject, when the topic changes? This way, it would be easier finding them in the future.

Thank you!

Title: Re: Could this be the holy grail ?
Post by: veritas on October 11, 2008, 05:01:16 pm

Leit,
Coupling current findings with data from earlier studies, Barton Haynes, MD, Director of CHAVI and the senior author of the study, believes that a successful vaccine would have to create immunity that would precede the time of infection, a process that might also involve manipulating the earliest antibody response and then sparking the stronger, broadly neutralizing response that normally occurs at a much later time in natural infection.   
 
"We are encouraged by these findings," says Haynes. "The pace of discovery is picking up and the pieces of the puzzle are coming together. Little by little we are learning more about the very earliest stages of HIV infection and a getting a clearer picture of what a successful vaccine will have to do."
 


The topic hasn't changed. This research is part of the vaccine antibody research being done at Duke. The quote above is the clue.

Title: Re: Could this be the holy grail ?
Post by: veritas on October 11, 2008, 07:41:36 pm

Abstracts from the Aids Vaccine 2008 conf.:


http://www.liebertonline.com/doi/pdfplus/10.1089/aid.2008.9997a

This pdf file is a long read.
Title: Re: Could this be the holy grail ?
Post by: veritas on October 13, 2008, 07:45:01 am

More anti-ps:


http://biz.yahoo.com/prnews/081013/lam040.html?.v=101
Title: Re: Could this be the holy grail ?
Post by: veritas on October 14, 2008, 04:16:14 am

Duke Human Vaccine Intiative (DHVI) - Who,What,Why:

http://humanvaccine.duke.edu/wysiwyg/downloads/DHVI_brochure_(website).pdf
Title: Re: Could this be the holy grail ?
Post by: veritas on October 15, 2008, 03:46:54 am

http://www.newsdaily.com/stories/tre49b1t8-us-aids-vaccine/
Title: Re: Could this be the holy grail ?
Post by: veritas on October 15, 2008, 04:23:05 am

"fair and balanced but still a bummer"





http://hosted.ap.org/dynamic/stories/A/AF_SOUTH_AFRICA_AIDS?SITE=AP&SECTION=HOME&TEMPLATE=DEFAULT&CTIME=2008-10-14-13-24-24
Title: Re: Could this be the holy grail ?
Post by: veritas on October 24, 2008, 09:27:29 am

The Hunt goes on:


http://www.dukemedmag.duke.edu/assets/articles/15338/The_Long_Hunt.pdf
Title: Re: Could this be the holy grail ?
Post by: veritas on October 29, 2008, 05:14:36 am

Latest patent from Duke University using broadly neutralizing antibodies and anti-ps for those already infected with hiv. A long read but exciting:


http://www.wipo.int/pctdb/en/wads.jsp?IA=US2008004709&LANGUAGE=EN&ID=id00000006940017&VOL=90&DOC=010f42&WO=08/127651&WEEK=43/2008&TYPE=A1&DOC_TYPE=PAMPH&PAGE=1
Title: Re: Could this be the holy grail ?
Post by: veritas on October 30, 2008, 09:27:21 am

excerpts from the patent:





Autoimmune disease patients can make antibodies that, in some capacity, have the ability to neutralize HIV-1 , either in binding to the HIV envelope or in binding to lipids on the surface of the virion, or both. Moreover autoimmune disease patients can make a protective neutralizing type antibody either constitutively or after HIV-1 infection.

The invention also includes antibodies from normal subjects and from autoimmune disease patients that do not react HIV envelope but rather with virus-infected cells and or virions, that is, they bind to lipid on the virus or virus-infected cells (see Example 6).


Example 6

Human monoclonal antibodies (termed CL1 , IS4 and IS6) derived from patients with anti-phospholipid syndrome have been studied.
IS4 and IS6 are pathogenic anti-lipid antibodies whereas CL1 is a non-pathogenic anti-lipid autoantibody (Table 4). Whereas none of these antibodies neutralized HIV pseudoviruses in the pseudovirus inhibition assay that reflects primarily infection by virion-cell fusion (Li et al, J. Virol. 79:10108-25 (2005) (Table 5), all three of these antibodies neutralized HIV-1 in the PBMC HIV neutralization assay that depends on endocytosis of HIV and is a mirror of HIV infectivity of CD4 cells in vivo (Table 6). That CL1 neutralized HIV evidences the facts that: a) humans can make non-pathogenic anti-lipid antibodies that neutralize HIV, and b) CL1 is an antibody that can be safely used as a therapeutic Mab for treatment of HIV infected subjects or in the setting of postexposure prophylaxis of subjects following needle, sexual or other exposure to HIV or HIV infected materials.

Alving and colleagues have made a mouse mab against phosphatidyl inositol phosphate and have shown that it neutralizes HIV in a PBMC assay (Wassef et al, MoI. Immunol. 21 : 863-868 (1984), Brown et al, Virol. 81 : 2087-2091 (2007), Beck et al, Biochem. Biophys Res. Comm. 354: 747-751 (2007)). What the present studies show is that humans can spontaneously make anti-lipid antibodies and that these antibodies can broadly neutralize HIV in an unprecendented manner.

Summarizing, autoimmune disease patients can make antibodies that bind to virus-infected cells and, presumably, to budding HIV virions by virtue of their reactivity to HIV membranes and host membranes. Certain anti-lipid antibodies from autoimmune disease patients can also react with the Envelope trimer (such as IS6) but not all of the antibodies react also with the trimer (i.e., CL1 and IS4 do not react). Therefore, reactivity with the HIV envelope is not a prerequisite for neutralization in these antibodies.

These studies also demonstrate that it may be possible to safely stimulate the production of CL1 like antibodies in humans using gp41 lipid complexes (Alam et al, J. Immunol. 178:4424-4435 (2007), Schuster et al, J. Immunol. 122:900-905 (1984)).

Title: Re: Could this be the holy grail ?
Post by: veritas on November 24, 2008, 04:02:53 am

more anti-ps:

  http://www.reuters.com/article/marketsNews/idINN2149745020081123?rpc=44
Title: Re: Could this be the holy grail ?
Post by: John2038 on November 24, 2008, 05:52:16 am
Eish  !
The immuno therapies sounds promising , what a time waste just for profit reasons, compared with having considered both approach simultaneously instead of just one
Title: Re: Could this be the holy grail ?
Post by: veritas on November 24, 2008, 07:50:13 am
I agree with you John. They should have gone after HIV right away. My only guess is that CHAVI was very interested in these mabs for both a cure and a vaccine  and they had the financial backing to do the necessary research. I believe we will be hearing a lot more about anti-ps in the very near future. I hope CHAVI has a homerun to report. Everyone needs their pound of flesh! IMHO.
(there is a lot more to this than the obvious).
Title: Re: Could this be the holy grail ?
Post by: veritas on November 24, 2008, 08:09:36 am
another view:


Data Published in Nature Medicine Highlights Ability of Peregrine Pharmaceuticals' Bavituximab to Cure Lethal Virus Infections

TUSTIN, Calif., Nov 24, 2008 /PRNewswire-FirstCall via COMTEX News Network/ --

--PS-Targeting Antibodies May Represent a Completely New Class of Drugs with Broad Potential to Treat Life-Threatening Viral Infections--

--Peregrine's Clinical-Stage Anti-PS Agent Bavituximab and Equivalent Antibodies Cured Lethal Viral Infections in Preclinical Models--

--Data Confirms PS is a 'Druggable' Target Common to a Number of Serious Viral Infections--

Peregrine Pharmaceuticals, Inc. (Nasdaq: PPHM) today reported publication of data in Nature Medicine that supports the broad anti-viral potential of the company's novel anti-phosphatidylserine (anti-PS) antibody platform, showing that its PS-targeting drug bavituximab can cure lethal virus infections in animal disease models.

Bavituximab is in clinical trials for the treatment of hepatitis C virus (HCV) infection and in preclinical development for the treatment of viral hemorrhagic fevers under a contract worth up to $44.4 million with the bioterrorism program of the U.S. Defense Threat Reduction Agency (DTRA). Bavituximab and other anti-PS antibodies are also being studied preclinically in HIV, cytomegalovirus (CMV) and other serious viral infections.

"Based on these findings, anti-PS antibodies such as bavituximab may represent a completely new class of drugs for the treatment of life-threatening viral infections," said study co-author Dr. Philip Thorpe, professor of pharmacology at UT Southwestern Medical Center and a scientific advisor to Peregrine. "By targeting a property of the host cell rather than the virus itself, anti-PS antibodies have the potential to treat a range of viral infections, and they should be less susceptible to the viral mutations that contribute to the development of drug resistance."

In the research reported today, scientists at UT Southwestern assessed the activity of bavituximab in animal models of two lethal viruses --cytomegalovirus and Lassa fever virus, a hemorrhagic fever virus that is listed as a class A bioterrorism agent by the CDC. Bavituximab showed potent anti-viral activity in both models.

Dr. Melina Soares, lead study author and UT Southwestern instructor of pharmacology, commented, "Recent non-affiliated research has further confirmed that exposed PS has immunosuppressive properties and is also clarifying its involvement during viral infection of cells. Our data go a step further, providing compelling evidence that exposed PS itself is a promising anti-viral drug target that is involved in the pathogenesis of multiple viruses, suggesting the possibility of achieving broad-spectrum anti-viral effects using a single anti-PS agent. We look forward to further exploring the potential of bavituximab and other anti-PS antibodies against viruses for which there are few or no effective therapeutic options."

In the first study, 100% of mice infected with lethal murine CMV and treated with bavituximab recovered fully, while only 25% of control animals survived. In the second study, guinea pigs were infected with lethal Pichinde virus, which is a model virus for Lassa fever. Fifty percent of the bavituximab-treated group survived, while untreated animals all died. In this study, the anti-viral effect of bavituximab was further augmented by the addition of the standard of care drug ribavirin, with 63% of animals receiving the combination therapy surviving the potentially lethal infection.

"We are extremely pleased to see this research demonstrating the broad anti-viral potential of bavituximab and our anti-PS technology platform published in this highly regarded journal," said Steven W. King, president and CEO of Peregrine. "This new publication is the latest in a series of external validations of our anti-viral program. It follows a recently awarded federal government contract for assessment of anti-PS antibodies to treat viral hemorrhagic fevers, research on the role of PS in viral infections that was published in a leading science journal earlier this year, and a recent presentation on anti-PS antibodies at a global HIV conference."

Anti-ps antibodies have already been tested in humans with top line safety data.
Title: Re: Could this be the holy grail ?
Post by: veritas on November 26, 2008, 04:05:21 am

Could this be the Holy Grail?


http://www.aidsmeds.com/articles/hiv_bavituximab_phosphatidylserine_1667_15688.shtml
Title: Re: Could this be the holy grail ?
Post by: fortuneseeker on November 26, 2008, 11:25:55 am
This Bavituximab: A New Strategy for Fighting Viruses..

Could be a very good and new approach to fight the virus perhaps..
And maybe it not be resistant...
Title: Re: Could this be the holy grail ?
Post by: veritas on November 26, 2008, 12:57:43 pm

Fortuneseeker,

The virus cannot mutate against bavituximab because the antibody does not go after the virus itself. It attacks the exposed phosphalipid attached to the virion and also to the reservoir cell that the virus has infected. This phosolipid flip on these cells are a primary function of the cell that occurs throughout the body when cells die. In order for the virus to escape this mechanism it would have to evolve to a different life cycle and that won't happen in our life time.

veritas
Title: Re: Could this be the holy grail ?
Post by: fortuneseeker on November 26, 2008, 06:33:29 pm
Thank you for information Veritas..
So indeed this could be something great in hiv treatment ?
Title: Re: Could this be the holy grail ?
Post by: Miss Philicia on November 26, 2008, 08:27:17 pm
Do you people even have HIV?
Title: Re: Could this be the holy grail ?
Post by: veritas on November 27, 2008, 04:39:16 am
Fortuneseeker,

I believe that this therapy will turn HIV therapy on its head. I don't believe that CHAVI would be interested in anti-ps if they didn't see something wonderful in it.

Philicia,

If you read the entire thread you would know the answer to your question. In a word , yes.

veritas
PS: I'm on the same drugs as you Philicia.
Title: Re: Could this be the holy grail ?
Post by: veritas on November 27, 2008, 10:11:33 am

More anti-ps, diff virus same moa:







Nat Med. 2008 Nov 23. [Epub ahead of print]Targeting inside-out phosphatidylserine as a therapeutic strategy for viral diseases.Soares MM, King SW, Thorpe PE.
Department of Pharmacology, 6001 Forest Park Road, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9041, USA.

There is a pressing need for antiviral agents that are effective against multiple classes of viruses. Broad specificity might be achieved by targeting phospholipids that are widely expressed on infected host cells or viral envelopes. We reasoned that events occurring during virus replication (for example, cell activation or preapoptotic changes) would trigger the exposure of normally intracellular anionic phospholipids on the outer surface of virus-infected cells. A chimeric antibody, bavituximab, was used to identify and target the exposed anionic phospholipids. Infection of cells with Pichinde virus (a model for Lassa fever virus, a potential bioterrorism agent) led to the exposure of anionic phospholipids. Bavituximab treatment cured overt disease in guinea pigs lethally infected with Pichinde virus. Direct clearance of infectious virus from the blood and antibody-dependent cellular cytotoxicity of virus-infected cells seemed to be the major antiviral mechanisms. Combination therapy with bavituximab and ribavirin was more effective than either drug alone. Bavituximab also bound to cells infected with multiple other viruses and rescued mice with lethal mouse cytomegalovirus infections. Targeting exposed anionic phospholipids with bavituximab seems to be safe and effective. Our study demonstrates that anionic phospholipids on infected host cells and virions may provide a new target for the generation of antiviral agents.

PMID: 19029986 [PubMed - as supplied by publisher]
Title: Re: Could this be the holy grail ?
Post by: veritas on December 01, 2008, 01:18:39 pm
anti-ps and bavituximab explained:

For years scientists have tried to combat viruses through the design of drugs targeting various molecules belonging to the viruses themselves. As logical and as promising as this may sound, the strategy has achieved limited success.

A new paper published in the journal Nature Medicine, detailing experiments performed by scientists from the University of Texas working for Peregrine Pharmaceuticals Inc., has surprisingly shown that instead of targeting a viral molecule, drugs targeting a particular non-viral tag-along fat which viruses grab from our own cell's plasma membrane, may be the most effective way yet to combat viruses - many different viruses. This cell membrane material gets stuck to viruses as they exit cells. The same material becomes exposed specifically on virally-infected cells, but not on healthy cells. The U. of Texas and Peregrine Pharmaceuticals work published in Nature Medicine shows that using an antibody to target this host-cell fat can cure typically lethal viral infections.

As a virus exits one of our cells, whether it's an influenza virus, or HIV, deadly hemorrhagic virus, hepatitis C, herpes virus, or many others, each virus takes along a little of the cell's greasy perimeter membrane as a coat. Normally, as part of a healthy cell, this perimeter membrane is made up of well-organized lipid molecules, with negatively charged lipids, specifically one termed "phosphatidylserine" (PS), sequestered to the inside of the membrane. This organization of membrane lipids requires a certain amount of energy, and consequently such organized lipids are only maintained in healthy cells. Viruses lack the ability to keep the lipid "PS" on the inside of their stolen lipid membrane. Unlike healthy cells, viruses are wearing inside-out lipid coats, and so are the cells that viruses infect. The negatively-charged lipid "PS" is exposed. That's the target.


Influenza and influenza-infected cells wear the PS target.
HIV and HIV-infected cells wear the PS target.
So do herpes viruses, as well as dangerous hemorrhagic fever viruses, and many others.

Multiple viruses and virally-infected cells are
all exposing the same lipid target.


The scientists designed an antibody, named Bavituximab (anti-PS), which is attracted to the negatively charged lipid PS. They found that the antibody binds to viruses and virally infected cells from multiple virus families. An antibody's job is to alert the immune system to destroy what it's attached to. In the case of anti-PS, the immune system is motivated to destroy the virus and virally-infected cells that expose PS. In the experiments detailed in Nature Medicine, animals receiving a lethal dose of a hemorrhagic fever virus were cured with anti-PS treatment. All animals not receiving anti-PS died from the infection.

Immunologists have found that exposed PS appears to provide a signal for a "host-friendly" immune response. Our own cells expose PS as a sign that they are dying. If a dying cell was left to decay in the body, it would eventually leak dangerous chemicals that could damage nearby cells, potentially causing a deadly cascade of cell death that could be harmful to the overall organism. Scientists have discovered that exposed PS appears to be the fundamental trigger for neighbor cells in the same organism as well as "professional" roving immune cells to perform a sort of "friendly clean-up". This clean-up procedure is much different from the way our immune system deals with what it perceives as foreign invaders. Exposed PS thus seems to send a signal to the cells of our immune system to NOT mount an attack. However, when the exposed PS is covered with the anti-PS antibody Bavituximab, it's as if the viruses and virally-infected cells are all wearing a big red flag, alerting the cells of the immune system to attack, and even to remain vigilant into the future to guard against any reappearance of the invader.

Concurrent to the recent insights gained by immunologists into the immuno-suppressive functions of exposed PS, scientists studying several different viruses have discovered that viruses contain PS exposed on their surface. The PS was taken from the cell they were 'born' from. Importantly, the most recent research, published in the journal Science, has demonstrated that the exposed PS on viruses is functional- it plays an essential part in the infection process. The PS is required for the virus to enter/infect new cells. Covering the PS, or removing the PS, prevents viral infection of cells.

These recent discoveries lead to a fascinating hypothesis. It seems that viruses have been taking advantage of our immune response to native dying cells. As multicellular organisms and viruses evolved together over time, successful viruses may have found and exploited our immune system's Achilles' heel. Now it seems that we may have found theirs, through targeting the very molecule that viruses have been stealing from the inside of our cell membranes to avoid an immune system attack.


Title: Re: Could this be the holy grail ?
Post by: J220 on December 02, 2008, 10:55:18 am
Very good article.
Title: Re: Could this be the holy grail ?
Post by: veritas on December 04, 2008, 08:12:51 am
India has found anti-ps:


http://anscreativity.blogspot.com/2008/12/new-drug-finds-viral-hiding-spots.html


scroll down.
Title: Re: Could this be the holy grail ?
Post by: veritas on December 05, 2008, 02:43:32 pm

CHAVI  moving forward:


CHAVI 005


led by Tony Moody, Director, Laboratory of B cell Immunology, Duke University

CHAVI 005 – Analysis of Host Response to HIV-1 in Autoimmune Disease Patients
The purpose of this study is to test a hypothesis for why broadly reactive neutralizing antibodies are predominantly absent during AHI. This protocol will screen patients with autoimmune diseases such as lupus or Anti-Phospholipid Antibody Syndrome who are co-infected with HIV in order to study the quality of anti-HIV neutralizing antibodies. The hypothesis is that patients with B cell tolerance defects will be able to make more robust anti-HIV antibody responses. This study has been approved and is currently underway.




1. Purpose of the study- This is a cross-sectional study that analyzes the sera of subjects in order to answer two clinical questions. First, we will assay the antibody profiles of subjects with autoimmune diseases to determine if there is cross-reactivity with the HIV epitopes 2G12, 1b12, 2F5 and 4E10, in addition to analyzing B and T cells to assess patterns that contribute to autoimmunity and autoantibody reactivity. The second goal of the study is to assess the prevalence of HIV infection in a cross-sectional cohort of subjects with autoimmune disease.




2. Background & significance – After twenty years of study, the HIV epidemic continues to rage world-wide. Now over 40 million people are infected and an estimated 100 million will be infected by the year 2010 (1). A safe and effective HIV vaccine is desperately needed. HIV vaccines have proven extremely difficult to develop. One of the most urgent problems to solve is to induce antibodies that broadly neutralize HIV of all subtypes. To date, 4 human monoclonal antibodies that broadly neutralize HIV, termed 2G12, 1b12, 2F5 and 4E10, have been made from HIV infected subjects (2-4). Anti-2G12 targets a carbohydrate determinate on HIV envelope protein gp120. Anti-1b12 binds to an epitope on the CD4 binding site, and anti- 2F5 and anti-4E10 recognize membrane-proximal epitopes of the envelope protein gp41 near the surface of the virion.


A conundrum has developed with the observation that while multiple envelope immunogens express these epitopes on the surface of the envelope trimer, after injection into animals or man, the epitopes are not immunogenic. Moreover, most patients who are infected with HIV do not routinely make antibodies to these targets. Thus a major effort is to learn how to induce broadly reactive neutralizing antibodies against HIV by immunizing with these epitopes. Recently we have turned our studies to examine abnormalities in the host that may prevent a robust humoral immune response to these conserved HIV epitopes. We have speculated that a critical host factor could be that the 2G12, 1b12, 2F5 and 4E10 epitopes are also self-antigens. Consequently, if host B cells generate antibodies against these HIV epitopes, they are immediately deleted because the antibodies are autoreactive. Supporting evidence for this hypothesis from our group has shown that antibodies raised against 1b12, 2F5 and 4E10 have potent cross-reactivity for autoantigens including double stranded DNA, Ro, phospholipids, centromere B, topoisomerase and histones.




The association between autoimmune disease and infection with human immunodeficiency virus (HIV) has evolved over the past two decades. Initial observations described spontaneous improvement in conditions including systemic lupus erythematosus (SLE) in patients that developed AIDS as a consequence of HIV infection. Since the advent of highly-effective antiretroviral therapy, new-onset autoimmune diseases or relapse of previous autoimmune diagnoses have been observed after recovery of CD4+ T cell counts. Although it is consistent with the known pathophysiology of autoimmune disease that a reduction in immune function, whether by therapeutic intervention or retroviral infection, should decrease disease activity, little has been reported on the overall prevalence of HIV infection in patients with autoimmunity. In fact, relatively few cases of systemic lupus erythematosus, the prototypical systemic autoimmune syndrome, have been described in the literature. Moreover, there are no reports of HIV prevalence among cohorts of subjects with defined autoimmune disease. More recently, the sense has grown that subjects with autoimmune disease experience less HIV burden than would be expected of the general population.


These clinical and laboratory observations have led to an exciting postulate that perhaps patients with autoimmune disease are protected from HIV infection due to their intrinsic loss of self-tolerance. Whatever the defect in central and/or peripheral tolerance that leads to the emergence of autoimmune disease may also permit these patients to generate neutralizing (auto-)antibodies against the HIV epitopes described above. To investigate this proposition, we plan to assess for the prevalence of HIV infection in the cohort of autoimmune disease-afflicted patients cared for in the Duke Rheumatology Clinic (particularly, the Duke Lupus Clinic and Duke Scleroderma Research Center). In addition, we will examine the reactivity of sera from subjects with autoimmune diseases including SLE, systemic sclerosis, Antiphospholipid antibody syndrome, and Sjogren’s syndrome. Serum reactivity will be analyzed for a broad panel of autoantigens (centromere, topoisomerase, extractable nuclear antigens (Smith, ribonucleoprotein, Ro, and La), double-stranded DNA, cardiolipin (phospholipids), histones) and the HIV epitopes (2G12, 1b12, 2F5 and 4E10). In addition, all subjects will be tested for HIV infection with HIV PCR. These results will be compared with those obtained from a healthy control group (n=100). As part of the protocol, separated B cells will be sent to Dr. James Robinson of Tulane University for manufacture of hybridomas. This technique will generate B cells that make antibodies targeting various HIV envelope antigens. Dr. Robinson will use the hybridomas to sequence interesting B cell DNA for analysis of immunoglobulin gene structure. In addition, anonymized samples of serum will be sent to Dr. George Shaw at the University of Alabama, Birmingham for performing HIV-1 neutralization assays.
















Title: Re: Could this be the holy grail ?
Post by: veritas on December 06, 2008, 09:35:35 am

This attached is amazing:

http://www3.niaid.nih.gov/Biodefense/PDF/tarvacin.pdf

Tarvacin is the old name for Bavituximab and it looks like the gov. thinks it's the holy grail. I strongly suggest you read the entire link. God I hope they have it!

veritas
Title: Bavituximab
Post by: tash08 on December 06, 2008, 03:10:23 pm
Bavituximab Anti-Viral represents a unique approach to treating viral diseases by recognizing features found only on infected cells and enveloped viruses. Bavituximab is a monoclonal antibody that binds to a basic component of the cell structure called an aminophospholipid that is exposed on the surface of cells only when they are infected with certain viruses or when they are malignant.

After binding to these infected cells, the drug alerts the body’s immune system to attack the infected cells. This makes infected cells particularly susceptible to bavituximab treatment, while potentially sparing healthy cells. Also, bavituximab binds to phospholipids which are derived from the host (human) cell and not the virus, which indicates it may not be susceptible to viral drug resistance. In addition to treating an active illness, bavituximab may also confer long-term immunity.

Peregrine has completed single and multiple ascending dose, monotherapy trials in patients with chronic HCV infection. Bavituximab infusion was generally well-tolerated and encouraging signs of anti-viral activity were seen at all dose levels tested. A Phase Ib study in patients co-infected with HCV and Human Immunodeficiency Virus (HIV) is now underway. This multi-center trial is designed to evaluate multiple doses of bavituximab for safety, pharmacokinetics and initial efficacy.


In pre-clinical experiments, Peregrine continues to evaluate bavituximab's potential for the treatment of several virus infections including influenza and HIV.

broken link removed
Title: Re: Bavituximab
Post by: freewillie99 on December 06, 2008, 03:29:11 pm
This post is a duplicate and should be merged with the "Could this be the holy grail" thread.
Title: Re: Could this be the holy grail ?
Post by: veritas on December 09, 2008, 01:26:00 pm


UK reports about Bavituximab:


http://drugdiscoveryopinion.com/
Title: Re: Could this be the holy grail ?
Post by: veritas on December 14, 2008, 04:22:54 am

More anti-ps pr:


http://www.scientificblogging.com/erin039s_spin/antiviral_motel_viruses_check_they_dont_check_out
Title: Re: Could this be the holy grail ?
Post by: leit on December 14, 2008, 12:12:14 pm
It attacks the exposed phosphalipid attached to the virion and also to the reservoir cell that the virus has infected.

Hi "veritas"!

To your knowledge, is there any scientific paper showing indisputably that also the resting cells of the reservoirs, which are in a unique condition, have their PS exposed? This is crucial, I think.
Thank you!

Title: Re: Could this be the holy grail ?
Post by: veritas on December 14, 2008, 06:42:31 pm

leit,

Please read the above " HIV - Phosphatidylserine Breakthrough " with references. In a word "yes". All cells invaded by the virus flip ps jnside out. So yes anti-ps should be able to go after resting cells. The trick is to generate the appropriate dosage to get them all. Anti-ps seems to teach the immune system
how to do this on its own (adaptive immunity). Your immune system goes everywhere. I believe if you read the entire thread your questions will be answered.

veritas
Title: Re: Could this be the holy grail ?
Post by: veritas on December 15, 2008, 05:17:04 am

leit,

Here's some backup research ----- not an easy read:


  http://www.jacionline.org/article/PIIS0091674908007252/fulltext


veritas
Title: Re: Could this be the holy grail ?
Post by: veritas on December 18, 2008, 12:58:45 pm

Vaccine research:


http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2276525
Title: Re: Could this be the holy grail ?
Post by: veritas on January 06, 2009, 04:50:00 am

Anti-ps is looking more promising:


http://www.peregrineinc.com/images/stories/media/siteFiles/PSbackgrounder.pdf
Title: Re: Could this be the holy grail ?
Post by: veritas on January 06, 2009, 04:54:22 am

Anti-ps again mentioned in Nature Mag.:


http://3.bp.blogspot.com/_ekJ44PA8pQc/SWI6NlyUlDI/AAAAAAAAAHY/_ADYeFKcSCM/s1600-h/Nature+reviews+Bavituximab+antiviral+with+logo.JPG
Title: Re: Could this be the holy grail ?
Post by: veritas on January 06, 2009, 08:15:09 am

For those of you who want to know more about Bavituximab that is presently in clinical trials for co-infection hepc and hiv and being studied at CHAVI at Duke University  (anti-ps) for both a therapeutic and vaccine please read:


http://www.peregrineinc.com/images/stories/media/siteFiles/20081121_BavituximabAV.pdf
Title: Re: Could this be the holy grail ?
Post by: hotpuppy on January 06, 2009, 11:34:19 pm
I have no interest in reading 97 pages of a .pdf file, but thanks.  I'll leave that to someone else here to do.


I have to agree.  This  type of post is annoying when there is just a link and a sensational subject.  It would be really NICE if people posted a short 2 or 3 sentence summary of the link.  That way I can decide if it is worth going and reading.

As a general rule, patent applications read like federal law.  Great for insomnia.
Title: Re: Could this be the holy grail ?
Post by: veritas on January 07, 2009, 09:25:53 am

hotpuppy,

This thread is dedicated to anti-ps therapy as it is progressing through the research stage and clinical trials. I realise that the science is difficult to understand and many of the studies herein are an effort to read without background info needed to understand their significance, however, by opening the links and reading both the heading and perhaps the first few sentences should give you an indication as to their content and you can then make a decision to read or not. Some readers don't want to follow the science this closely and I can appreciate that, however there are readers of this thread who do want to know what the status of the science is and believe as I do that anti-ps is  very promising. The "sensational headings" as you call them make sense if you read the link and have been following the thread and understand the moa (method of action ) of the antibody. I tried to explain the moa in an earlier post to Miss philicia. If you have any questions regarding the science I will try to answer however, everyone has to make up their own minds as to the merit of the science and the links. It is your decision to read or not to read.

veritas
Title: Re: Could this be the holy grail ?
Post by: hotpuppy on January 07, 2009, 12:17:29 pm
I'm just suggesting that you will share information with more people if you do more than post a link.

Posting an enticing headline with a link constitues a tease online.  It annoys most internet users.  It's the online equivalent of having a candy bar wrapper, nicely sealed, that says "yummy treat inside" and when you open it, all that is inside is a coupon and directions to a local store.  It would piss you off.  It's a broken expectation.

The thread should be titled: Anti-PS Therapy update

It's sensationalist to call anything a holy grail.  But you call it what you want.  It simply discredits you as a reliable source when you set and break expectations.

an example of what I'm suggesting is:

"link here"

I found an article about (what), that is important because (why), and is an exciting update (your reason).

That gives someone who clicks on the thread an idea of what you found and makes you helpful.

The science is really not that difficult to understand.  The summary is really easy, here I'll do one:

Researchers are targeting a chemical called Phosphatidylserine (PS).  PS normally occurs inside the cell, however in virus infected cells it shows up on the outside of the cell.  Reserachers think that they can leverage this with new treatments that target PS, and thus the virus infected cells.  Researchers believe that they can get to latent reservoirs using this technique.


**** Next link
  http://www.jacionline.org/article/PIIS0091674908007252/fulltext

This link covers basic HIV-1 immunology and vaccine background theory.  Of particular interest are the infection timeline which clearly shows why early intervention and treatment are advantageous.  It gives a theorized timeline for when latent cells are formed in one graph.

Another paragraph in this article discusses the link between cd4 depletion and progression to AIDS.  Interesting reading if you are interested in vaccine development or background HIV theory.

*** end example.

Not that hard and shows respect for others like Ms. Phillicia who may not want or have time to read everything.  It gives her enough information to make an informed decision about whether they want to read someone's doctoral power point http://www3.niaid.nih.gov/Biodefense/PDF/tarvacin.pdf (very cheesy graphics and clearly a justification presentation).

The easier you make it for others to understand what you are sharing, the more people will appreciate it. 
Title: Re: Could this be the holy grail ?
Post by: veritas on January 07, 2009, 12:57:10 pm
hotpuppy,

I'll give you an example of not fully under standing the moa of the antibody and its potential implications: That simplistic powerpoint with the "chessy graphics" that you referred to was presented to the Dept of Defense for their biological threat initiative. The presentation earned the company developing this therapy a 44million dollar contract for further development in conjunction with the dept of defense.

I also see that you were able to quickly read the links and get the jist of the information. If you can do it then shouldn't others be able ito do the same?
By the way, I purposely used the Holy Grail analogy with the "Could "proviso because should the antibody prove to work in humans as it did in preclinicals then we have a cure and a vaccine. That would be the HOLY GRAIL! 

veritas
Title: Re: Could this be the holy grail ?
Post by: georgep77 on January 07, 2009, 05:02:31 pm
I completely agree with you veritas, thanks for your research news....

                                              :D
Title: Re: Could this be the holy grail ?
Post by: hotpuppy on January 07, 2009, 11:31:36 pm
I also see that you were able to quickly read the links and get the jist of the information. If you can do it then shouldn't others be able ito do the same?
By the way, I purposely used the Holy Grail analogy with the "Could "proviso because should the antibody prove to work in humans as it did in preclinicals then we have a cure and a vaccine. That would be the HOLY GRAIL! 

1.  You can continue to post a link only.  I'm just pointing out that you will be useful to alot more people when you post some information about the link.  Being narrowminded and rude is your right.  Just remember not everyone has a good internet link, a good computer, or the time to wade through research.

2. Just because you and I are capable of reading through collegiate and scientific research does not mean that others on here are.  Locking them out is wrong.  The goal of the forums is to help others and a big part of helping is sharing knowledge in a format that makes it accessible to others.

3. I think it's sensationalist to call something a holy grail or cure.  The papers you linked to clearly indicate that there are substantial and real obstacles.  Anti-PS and monoclonal AB are two paths that researchers are evaluating.  Four years ago we were "assured" that an effective vaccine was just around the corner.  In 1985 (or maybe 83) the CDC promised us a vaccine in 2 years.  (See PBS Frontline 2006 AIDS History - paraphrased title - 2 hour DVD program on AIDS History). 

4. While you may think otherwise, 44 million doesn't go far in research.  Especially government funded research.  I still think it's a

5. If you want a functional vaccine.... we already have the resources.  http://www.medpagetoday.com/MeetingCoverage/ICAAC/6719  Dr. Jacobson states what I suspected.  Entry inhibitors can provide an effective barrier to R5 infection.  This would stop, at a minimum, 60 to 70% of the infections.  Probably not cheap, probably not as convenient as a shot, but a definate, viable option with few side affects.  When it comes to treatments, I'm afraid that a pill is going to win out over anything that looks like a genetically engineered treatment... at least in the short term.  The only problem is that it isn't a classical vaccine, and we are not likely to succeed with a classical vaccine. 

Title: Re: Could this be the holy grail ?
Post by: veritas on January 08, 2009, 05:46:56 am

Hotpuppy,

I suggest you do more research into PRO140. You will find that the antibody must  be redosed perpetually to keep the virus ud and does nothing for the hidden or latent cells. Anti-ps will not only eliminate free-flowing virus but will also eliminate latent virus without perpetual dosing since it has the potential to teach your immune system to do the job on its own (adaptive immunity).Yes- more research has to be done to obtain or prove that goal in humans - maybe a second generation mab has to be developed- but the fact remains it did occur in animal models and was picked by the CHAVI group as the basis of their research for a cure and a vaccine.
That 44million dollars is only a small part of the research dollars going into anti-ps.CHAVI alone has received well over 300million from the Bill and Melinda Gates foundation for their research for a cure and a vaccine and of course the additional dollars poured into the research by other institutions(utsw,Duke,Harvard,pphm etc.). By the way I believe the 44million was the largest grant given by the DOD or the second largest.
Hotpuppy, if you would like to join me in developing this thread for the benefit of all readers, then I will gladly find the links and you can paraphrase for all. But remember that those without a good internet link or a good computer  will still not be able to go to the original docs if your paraphrasing sparks their interest.
Furthermore there is a big difference between something being  the holy grail and asking the question could this be the holy grail.

veritas
Title: Re: Could this be the holy grail ?
Post by: veritas on January 08, 2009, 08:13:41 am

Interesting interview by Charlie Rose with Anthony Fauci and David Ho. I wonder what the viral shield from the immune system  is that their talking about?


http://www.charlierose.com/view/interview/9861
Title: Re: Could this be the holy grail ?
Post by: bmancanfly on January 08, 2009, 08:43:41 am
thanks for your posts Hotpuppy.
Title: Re: Could this be the holy grail ?
Post by: leit on January 08, 2009, 07:06:31 pm

I wonder what the viral shield from the immune system  is that their talking about?
http://www.charlierose.com/view/interview/9861

I think they refer to envelope proteins' sugar coating.
Anyway, what a cheerlessness!  :(

Title: Re: Could this be the holy grail ?
Post by: leit on January 08, 2009, 08:20:29 pm

Anti-ps [...] will also eliminate latent virus

I'd be not so sure of that: resting HIV infected cells are in a very unique condition and, to the best of my knowledge, it's nowhere stated whether they expose PS or not.

Quote
it has the potential to teach your immune system to do the job on its own (adaptive immunity).

I don't think so: The immune system attacks virions and cells that bavituximab has bound to ONLY BECAUSE it's alerted by bavituximab itself! If a possible adaptive immunity against a SPECIFIC virus (targeted by bavituximab) develops, it's because bavituximab, blunting the infection, gives the immune system TIME to mount SPONTANEOUSLY an effective response before the host is killed. But, since the immune system has proven itself incapable of mounting such a response against HIV, I doubt that bavituximab can make a difference.

That said, if bavituximab will be able to bind to ALL reservoirs' cells, bavituximab + HAART would very probably be the "holy grail": ERADICATION.

Title: Re: Could this be the holy grail ?
Post by: veritas on January 09, 2009, 05:16:18 am

leit,

Please read the attached explaining anti-ps in depth with the appropriate references:

http://www.peregrineinc.com/images/stories/media/siteFiles/PSbackgrounder.pdf

PS is located in every cell of the human body. When the cell is infected with some type of pathogen,the cell can no longer hold ps pointing inward (ps flips outward). This flip is a naturally occuring process in the human body when cells are dieing and the immune system leaves them alone. By the way,this flip also occurs in cancer cells. Bavituximab alerts the immune system to this deception and calls the immune system in for the kill.

As far as adaptive immunity is concerned, mice infected with the cmv were treated with Bavituximab and cured. Upon rechallenge by a lethal dose of the virus, the mice were able to fight off the virus on their own with no further dosing of Bavi.
Is Bavituximab THE mab that is going to work? I don't know. the research will tell the story. Perhaps a second generation mab will have to be developed to mount a stronger immune response.

You seem to be interested in the science, so please read the above pdf in depth and let me know what you think. The science is exciting.

veritas
Title: Re: Could this be the holy grail ?
Post by: veritas on January 09, 2009, 08:14:56 am

leit,

After reading the above link on anti-ps, here is another link on Bavituximab:


http://www.peregrineinc.com/images/stories/media/siteFiles/20081121_BavituximabAV.pdf

Both these links have been posted before. This second link is a much easier read on Bavituximab but should be read after reading the anti-ps pdf.


veritas
Title: Re: Could this be the holy grail ?
Post by: veritas on January 09, 2009, 08:21:55 am

leit,

After reading the previous then read this:

http://www.scientificblogging.com/erin039s_spin/antiviral_motel_viruses_check_they_dont_check_out
Title: Re: Could this be the holy grail ?
Post by: veritas on January 09, 2009, 08:45:09 am



leit,

Then finally read this which is a very important presentation made to NIH then DOD which shows the adaptive immunity component in preclinicals:

http://www3.niaid.nih.gov/Biodefense/PDF/tarvacin.pdf

It was the lassa fever model that showed the adaptive immunity not cmv.

Have I answered your questions?

I'm very exicited about this research and truly believe that this is a breakthrough that we have been waiting for. If the immune response from Bavi is not strong enough to cure, then we will have towait for a second generation mab which I believe they are working on in conjunction with Duke University(please refer to the patents posted at the beginning of this thread). Even if Bavi doesn't cure, we will have I believe a damn good therapy with very few if any side effects since it has shown top line safety data in all humans tested to date(more than 100 for both virus and cancer).

This research is definitely a watcher!

veritas
Title: Re: Could this be the holy grail ?
Post by: veritas on January 09, 2009, 12:32:32 pm
More evidence of anti-ps as a safe therapeutic for various viral diseases:


http://microbiologybytes.wordpress.com/

"cellular toxicity by the virus led to the exposure of ps".

Direct clearance of infectious virus from the blood and antibody-dependent cellular cytotoxicity of virus-infected cells seemed to be the major antiviral mechanisms.
Title: Re: Could this be the holy grail ?
Post by: veritas on January 09, 2009, 12:59:19 pm
I think they refer to envelope proteins' sugar coating.
Anyway, what a cheerlessness!  :(


leit,
I agree the interview was cheerlessness but I was being somewhat facetious when asking what the shield was. Flipped PS shields the virus from the immune system. I believe both researches are being very cautious about what they say,thus the cheerlessness.

veritas
Title: Re: Could this be the holy grail ?
Post by: bimazek on January 10, 2009, 05:15:48 am
i havent read all of this but it looks very good
extremely exciting stuff

35 years ago or however long ago the first idea of a Mab monoclonal anti body was thought of, at that time they were suppose to be the holy grail of many diseases it just took alot longer to develop all of them for many diseases than science thought

i just posted a list of Mab that treat diseases in living with hiv section

supposedly theoretically they should have zero or low side effects or at least many orders of magnitutude less than chemical meds,

do you all understand difference between a chemical med and a Mab, monoclonal antibody

anyway

very very good news

i think this would be considered the best news i have seen in years

why because it is a Mab

and i remember 20 or 30 years ago or more Mab's were suppose to be the thing that would treat disease safely effectively without poisoning the human body

these are

fully human monoclonal antibodies folks, that means that they are as perfect as homo sapien, i mean yes there may be a few who have very unusual genetic make up who would have a reaction but since they are build in the form of human antibodies this should be very low

first thing is read the definition of all these terms in wiki to  get idea

nti-PS and monoclonal AB are two paths that researchers are evaluating.

keep posting

like where are the trials!!!!!!

i think we should all do some kind of protest when it gets thru 3rd phase demanding

wide spread use of this in usa

esp. since so many have so so so so many terrible side effects from the meds

i totally support HAART and no one should stop taking it unless discussed with thier doctor
and in my opinion everyone should start as soon as they find out poz if they have any problems, mental confusing can be sign of hiv in body, as well as any of the t cells under 500 should start asap

anyway

thanks
Title: Re: Could this be the holy grail ?
Post by: bimazek on January 10, 2009, 05:25:12 am
http://www.peregrineinc.com/index.php?option=com_content&task=view&id=30&Itemid=46
animaitons  and video


is this amazing link with animation anywhere on this post??

my eyes are getting weaker and seeing text is harder than in past

this has amazing stuff

http://www.peregrineinc.com/index.php?option=com_content&task=view&id=20&Itemid=36
Title: Re: Could this be the holy grail ?
Post by: bimazek on January 10, 2009, 06:00:28 am
could  DNA-altered animals produce fully human monoclonal antibodies?  I think they can right???

New old-fashioned drug makers: goats
Los Angeles Times - 2 hours ago
A herd has been genetically engineered to make a human protein in their milk that can prevent dangerous blood clots. If the drug is approved by the FDA, the barn door could swing open.
US advisers back 1st drug from DNA-altered animals Reuters

http://www.latimes.com/news/nationworld/nation/la-sci-geneticmilk10-2009jan10,0,242781.story

http://uk.reuters.com/article/scienceNewsMolt/idUKTRE50873T20090110
Title: Re: Could this be the holy grail ?
Post by: veritas on January 10, 2009, 06:04:47 am

Bim,

Thanks for your kind words.

Those video links are amazing and I thank you for posting them.

They are doing the combination HepC/Hiv trial but I believe they are leaving the strictly HIV trials to CHAVI. I also believe that CHAVI is going for the "Homerun" so its a matter of waiting for CHAVI to release information. Since CHAVI is under a microscope (media wise), they seem to do testing 9 ways to Sunday before releasing any information. That's a good thing I guess but the wait is frustrating.

Your absolutely right when it comes to mabs vs chemicals, however, mabs can somtimes have adverse effects (WHEN YOUR IMMUNE SYSTEM ATTACKS YOUR OWN BODY).Usually,I believe, areaction like that happens fairly quickly but all mabs should be developed with caution. Bavituximab has shown no adverse reactions and as a matter of fact has shown top line safety data in trials thus far in humans.
I will definitely be following this research closely and please if you find any more info don't hesitate to post, your contributions are welcome and appreciated.

veritas
Title: Re: Could this be the holy grail ?
Post by: veritas on January 10, 2009, 09:14:05 am

A picture of the virus with PS exposed. This virus is in us:


http://3.bp.blogspot.com/_ekJ44PA8pQc/SWeCOeLgrrI/AAAAAAAAAIw/59sk3u6FiqU/s1600-h/HIV+virion.JPG
Title: Re: Could this be the holy grail ?
Post by: leit on January 10, 2009, 08:36:03 pm

Have I answered your questions?

Dear "veritas",

I had already read what you mentioned (and more), but...

I'm NOT interested in bavituximab IN ITSELF, nor in bavituximab & cancer, nor in bavituximab & CMV, nor in bavituximab & HCV... nor even in bavituximab & HIV, but ONLY in bavituximab & HIV RESERVOIRS.
Moreover, I think that trying to infer something from "bavituximab & X" is only wasted time, if "X" is not "HIV RESERVOIRS".

That said, I can only repeat that it's nowhere stated whether HIV latent reservoirs' cells expose PS or not and, consequently, whether bavituximab could be effective against them or not.
Since this is THE problem (HIV infection is still incurable only because of reservoirs, otherwise HAART would be enough), Peregrine Pharmaceuticals' silence on the matter arouses my suspicions.


Current trials confirm that. Please look at http://clinicaltrials.gov/ct2/show/NCT00503347 (http://clinicaltrials.gov/ct2/show/NCT00503347):

Bavituximab Repeat-Dose Trial in Patients Co-Infected With Chronic Hepatitis C Virus and Human Immunodeficiency Virus

Secondary Outcome Measures:
- Blood levels of [...] HIV RNA

Inclusion Criteria:
- Chronic hepatitis C infection based on history and detectable serum HCV RNA

Exclusion Criteria:
- [...] HIV antiviral therapy within 4 weeks of Day 0


If they would have meant to prove effectiveness of bavituximab on reservoirs, what above should have read:

Bavituximab Repeat-Dose Trial in Patients Infected With Human Immunodeficiency Virus

Secondary Outcome Measures:
- Blood levels of HIV DNA

Exclusion Criteria:
- Chronic hepatitis C infection based on history and detectable serum HCV RNA

Inclusion Criteria:
- Viral load < 50 copies/ml for at least the previous 12 months (*)
- Taking HAART (*)

(*) From: Valproic Acid and Its Effects on HIV Latent Reservoirs (http://clinicaltrials.gov/ct2/show/NCT00289952)


Bottom line: Peregrine Pharmaceuticals' folks seem to be the first who don't believe in bavituximab potential against reservoirs.
Title: Re: Could this be the holy grail ?
Post by: J220 on January 10, 2009, 10:23:45 pm

Bottom line: Peregrine Pharmaceuticals' folks seem to be the first who don't believe in bavituximab potential against reservoirs.

Why would they have it listed as a secondary outcome if they did not believe it may have potential? If it was not part of the clinical protocol and target for the trial they would not even mention it.
Title: Re: Could this be the holy grail ?
Post by: leit on January 10, 2009, 10:42:53 pm
"It" WHAT, please, "J220"???

Title: Re: Could this be the holy grail ?
Post by: J220 on January 10, 2009, 10:48:41 pm
The effect on reservoirs....//////////
Title: Re: Could this be the holy grail ?
Post by: leit on January 10, 2009, 11:00:46 pm

The effect on reservoirs is measured through HIV-DNA, not HIV-RNA.
Title: Re: Could this be the holy grail ?
Post by: J220 on January 10, 2009, 11:08:28 pm
Uhh, yeah, but if you are on HAART, you nevertheless have low-level replication. If after starting this therapy the levels of RNA are reduced or dissapear, what do you think the reason for this could be? In addition, the company specifically talks about the potential of this therapy in regards to HIV-infected cells and enveloped viruses. Listen, no one is telling you to believe this can work, but it's a large leap to say that Peregrine doesn't believe in the potential address reservoirs. What else do you think they are talking about?
Title: Re: Could this be the holy grail ?
Post by: veritas on January 11, 2009, 07:35:03 am

leit,

latent cell reservoirs are resting cd4 cellls infected with the virus non-replicating.Any cell in the body that is infected with the virus flips Ps. (see the video posted by Bimazek). PS does not flip back when the cell is resting. Also, the exposed ps is protecting the infected cell from the immune system.
J220 gets it.
The problem is going to come in the form of mounting a strong enough antibody response to eradicate the virus. However, if the mab is able to teach the immune system how to go after flipped ps on its own, like it did in the mouse models,our discussion could be a mute point. The research will tell.

veritas

Title: Re: Could this be the holy grail ?
Post by: veritas on January 11, 2009, 07:50:55 am
Please read this again:


Nature Reviews Drug Discovery 8, 19 (January 2009) | doi:10.1038/nrd2788

http://www.nature.com/nrd/journal/v8/n1/full/nrd2788.html

Antiviral Drugs: Exposed target for broad-spectrum antivirals
Man Tsuey Tse

Phosphatidylserine, the most abundant anionic phospholipid of the plasma membrane, has been used as a target to develop a novel broad-spectrum antiviral agent called bavituximab. Strikingly, bavituximab was able to cure overt disease in guinea-pigs infected with a potentially lethal dose of Pichinde virus, a model of Lassa fever virus.

Writing in Nature Medicine, Thorpe and colleagues proposed that the effects of a wide range of viruses on host cells could lead to normally intracellular anionic phospholipids being exposed on the surface of infected cells. To test this hypothesis, they used bavituximab — a chimeric antibody that binds to complexes of the phosphatidylserine-binding plasma protein 2-glycoprotein 1 and anionic phospholipids. These experiments showed that infection of mouse cells by Pichinde virus led to phosphatidylserine exposure, and that bavituximab binds to virus-infected cells and infectious virions.

Treatment of guinea-pigs infected with a normally lethal dose of Pichinde virus with bavituximab 6–7 days after infection led to 50% of the animals surviving, and clearance of the virus was observed by day 135. In addition, combination of bavituximab with ribavirin (the current drug of choice for treating Lassa fever) had an additive effect.

The authors also provided evidence for two mechanisms that seem to underlie these effects. First, bavituximab treatment clears infectious virus from the bloodstream. Second, it induces antibody-dependent cellular cytotoxicity of virus-infected cells. As the authors propose, it seems that phosphatidylserine on virions and infected cells might enable viruses to evade immune recognition and dampen inflammatory responses, and that bavituximab interferes with this 'masking' process.

Finally, the authors explored phosphatidylserine exposure in other viral infections. Exposure was also observed in cells infected with influenza virus, vaccinia, vesicular stomatitis virus and mouse cytomegalovirus (CMV). This indicates that this process is a common feature of enveloped viruses; exposure could also extend to non-enveloped viruses. Furthermore, tests in mice infected with an almost lethal dose of CMV showed that all treated mice survived, in contrast to untreated mice, of which only 25% were alive after 96 days.

In both animal models, bavituximab was well tolerated, and no toxicity was observed histologically. Therefore, targeting phosphatidylserine shows promise as an antiviral strategy. In addition, as phosphatidylserine is a host-derived target, the development of resistance could be limited. Clinical trials of bavituximab are currently underway in patients with hepatitis C co-infected with HIV.

References and links
ORIGINAL RESEARCH PAPER
Soares, M. M., King, S. W. & Thorpe, P. E. Targeting inside-out phosphatidylserine as a therapeutic strategy for viral diseases. Nature Med. 23 Nov 2008 (doi: 10.1038/nm.1885)
Title: Re: Could this be the holy grail ?
Post by: leit on January 11, 2009, 06:53:05 pm

if you are on HAART, you nevertheless have low-level replication. If after starting this therapy the levels of RNA are reduced or dissapear, what do you think the reason for this could be?

We are not playing hide-and-seek! The reservoirs' marker is HIV-DNA, not HIV-RNA. Period.

Quote
In addition, the company specifically talks about the potential of this therapy in regards to HIV-infected cells

HIV-infected cells are not necessarily resting latently infected cells (i.e. reservoirs). In fact, they behave very differently.

Quote
it's a large leap to say that Peregrine doesn't believe in the potential address reservoirs. What else do you think they are talking about?

About one of the many drugs which do nothing against reservoirs.
Title: Re: Could this be the holy grail ?
Post by: leit on January 11, 2009, 07:07:58 pm

latent cell reservoirs are resting cd4 cellls infected with the virus non-replicating.Any cell in the body that is infected with the virus flips Ps.

WHEN does it flip it? When HIV fuses with the receptors, when it actually enters the cell, when it reverse-transcripts its RNA into DNA, when this DNA integrates into the cell genome... when new virions bud out? WHEN EXACTLY?
If this "when" is "at the very beginning", then bavituximab could be fully effective against reservoirs, otherwise not (a T cell can become resting in any moment).

Quote
The problem is going to come in the form of mounting a strong enough antibody response to eradicate the virus.

The problem is whether ALL (if ANY!!!) reservoirs' cells expose PS, so that bavituximab can bind to them.

Quote
if the mab is able to teach the immune system how to go after flipped ps on its own, like it did in the mouse models

I've already told you that bavituximab teaches NOTHING. The mice developed SPECIFIC immune responses against SPECIFIC viruses only because bavituximab, blunting the infection, gave them time to SPONTANEOUSLY do that before they were killed by those viruses.
The only thing bavituximab can teach the immune system is to develop anti-chimeric antibodies that render bavituximab itself completely ineffective; definitely not a good lesson!
Title: Re: Could this be the holy grail ?
Post by: veritas on January 12, 2009, 05:39:35 am
WHEN does it flip it?

The problem is whether ALL (if ANY!!!) reservoirs' cells expose PS, so that bavituximab can bind to them.

I've already told you that bavituximab teaches NOTHING. The mice developed SPECIFIC immune responses against SPECIFIC viruses only because bavituximab, blunting the infection, gave them time to SPONTANEOUSLY do that before they were killed by those viruses.
The only thing bavituximab can teach the immune system is to develop anti-chimeric antibodies that render bavituximab itself completely ineffective; definitely not a good lesson!

PS flips as soon as the virus enters the cell due to cellular stress. (see video)

Bavi should be effective against the reservoirs if the immune response is strong enough.

The infection is not blunted but destroyed by the immune system by Bavi.s call to arms. (see video)

Please provide reference where Bavi is ineffective due to the development of anti-chimeric antibodies. If that were the case then redosing Bavi would be a problem as they are doing in clinical trials. It would have been interesting to see if that mouse cured with lassa fever had been rechallenged with a different retrovirus to see if the immune system was able to fight it off. Maybe they are doing it. But if Bavi or some next generation Bavi is being developed for bio-terrorism, then I guess the immune system can be TAUGHT to recognize exposed ps.

Title: Re: Could this be the holy grail ?
Post by: veritas on January 12, 2009, 09:31:52 am

Aids Vaccine Conference 2008: summary from NIAD



http://www3.niaid.nih.gov/topics/HIVAIDS/Research/vaccines/reports/aidsvac2008.htm


Broadly neutralizing antibodies take center stage and a better BAVI is talked about (antibody- 2G12).

Title: Re: Could this be the holy grail ?
Post by: veritas on January 13, 2009, 05:00:16 pm
Vaccine research pre-clinical - the vaccine worked in monkeys using mabs:

I forgot to add the reference (was too excited)

Long-term vaccine protection from AIDS and clearance of viral DNA following SHIV89.6P challenge


http://www.ncbi.nlm.nih.gov/pubmed/19135115?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

Schell J, Rose NF, Fazo N, Marx PA, Hunter M, Ramsburg E, Montefiori D, Earl P, Moss B, Rose JK.
Yale University School of Medicine, New Haven, CT, United States.

In an earlier study, our group vaccinated rhesus macaques with vesicular stomatitis virus (VSV) vectors expressing Gag, Pol, and Env proteins from a hybrid simian/human immunodeficiency virus (SHIV). This was followed by a single boost with modified vaccinia virus Ankara (MVA) vectors expressing the same proteins. Following challenge with SHIV89.6P, vaccinated animals cleared challenge virus RNA from the blood by day 150 and maintained normal CD4 T cell counts for 8 months. Here we report on the long-term (>5-year post-challenge) status of these animals and the immunological correlates of long-term protection. Using real-time PCR, we found that viral DNA in peripheral blood mononuclear cells (PBMCs) of the vaccinees declined continuously and fell to below detection (<5copies/10(5)cells) by approximately 3 years post-challenge. SHIV DNA was also below the limit of detection in the lymph nodes of two of the four animals at 5 years post-challenge. We detected long-term persistence of multi-functional Gag-specific CD8(+) T cells in both PBMCs and lymph nodes of the two protected animals with the Mamu A*01(+) MHC I allele. All animals also maintained SHIV89.6P neutralizing antibody titers for 5 years. Our results show that this vaccine approach generates solid, long-term control of SHIV infection, and suggest that it is mediated by both cytotoxic T lymphocytes and neutralizing antibody.
Title: Re: Could this be the holy grail ?
Post by: leit on January 14, 2009, 12:10:26 am

PS flips as soon as the virus enters the cell due to cellular stress. (see video)

Sorry, but I trust no longer in "WMF-drugs", nor in "Flash-drugs" (http://www.virxsys.com/pages/human-therapies/first-clinical-application/how-vrx496-works.php), nor in (fraudulent!) "Real-drugs" (http://www.koronispharma.com/VDA_large.rv). Peer-reviewed publications, please!

Quote
Please provide reference where Bavi is ineffective due to the development of anti-chimeric antibodies.

At the moment I cannot, nor I said this will happen. But, unfortunately, that's not an uncommon immune reaction against chimeric antibodies like bavituximab.

Quote
if Bavi or some next generation Bavi is being developed for bio-terrorism, then I guess the immune system can be TAUGHT to recognize exposed ps.

NO! Bavituximab teaches NOTHING! It is NOT an antigen which arouses a WHOLE and PERMANENT anti-viral immune response againt PS-exposing viruses, but only an antibody which, WHEN injected, annihilates viruses and infected cells CURRENTLY exposing phosphatidylserine.

Title: Re: Could this be the holy grail ?
Post by: veritas on January 14, 2009, 09:50:24 am

leit,

Did you read this post above?

HIV - Phosphatidylserine Breakthrough

That post has all thepeer review
you need if one bothers to read the references.


"At the moment I cannot, nor I said this will happen. But, unfortunately, that's not an uncommon immune reaction against chimeric antibodies like bavituximab."

You will not find any with Barvituimab!


"NO! Bavituximab teaches NOTHING! It is NOT an antigen which arouses a WHOLE and PERMANENT anti-viral immune response againt PS-exposing viruses, but only an antibody which, WHEN injected, annihilates viruses and infected cells CURRENTLY exposing phosphatidylserine."

Bavituximab does NOT annihilate viruses and infected cells exposing PS! Barvi alerts the immune system to annihilate viruses and infected cells exposing ps. Please do somemore research on the moa of Bavi.


Title: Re: Could this be the holy grail ?
Post by: leit on January 14, 2009, 05:57:41 pm

Ok, "veritas", now I'm fed up.

Good luck to you and to your messed-up personal, imaginary bavituximab!

Title: Re: Could this be the holy grail ?
Post by: veritas on January 15, 2009, 03:47:46 am

  Never go to war unarmed!
Title: Re: Could this be the holy grail ?
Post by: georgep77 on January 15, 2009, 08:25:36 am
Lol

              :D

           The time will tell, the winner of this battle
Title: Re: Could this be the holy grail ?
Post by: David Evans on January 15, 2009, 10:53:23 am
I'm not sure what the point of this whole "battle" is other than egos. Veritas and Leit are both arguing with a level of certainty that kind of astonishes me. It reminds me of the drunken/stoned philisophical arguments that seemed kind of interesting in Freshman year of college, but look silly now in hindsight.

The research on PS and bavituximab is in it's infancy. The sign of any researcher worth his or her salt is not the religious fervor and certainty with which they argue for a pet theory, but the ability to make a reasoned statement, after addressing the caveats. I hear no caveats.

Veritas is correct, as far as the research can tell us so far, that the PS does appear to flip with some infectious agents (not all), for reasons that are not yet clearly spelled out. What the scientists are proposing still needs to be more completely validated. There's some good data, but some it is also theory at this point. Bavituximab also appears, so far, to assist the immune system in recognizing these infected cells that would otherwise escape notice. It seems likely that this would apply to latently infected cells as well, but that's still theoretical until the clinical trials are conducted. That's about as far as anyone can go, based on the research that's been conducted so far.

The molecular interplay between the immune system and HIV is far too complex to do more than theorize any of the rest of it at this point. We've all seen even more promising and well documented HIV research amount to nothing, because of unanticipated complications. I'd encourage you guys to cool your jets on this until more clinical and basic research becomes available.

-David
Title: Re: Could this be the holy grail ?
Post by: veritas on January 16, 2009, 06:32:39 am
David,

I appreciate your intervention to allow calmer heads to prevail in explaining the potential of anti-ps as a therapeutic and vaccine. Escalation of emotion is never a good thing when discussing science, especially science that has not been proven 100% to date. That being said, I would like to further explain my position and also take issue with a few points. 
 I have been following Dr. Philip Thorpe's research on anti-ps since the late 90s. He is the inventor of the device. The science has been put through its paces in vitro and completed for both viral and cancer indications in the form of the 3g4 antibody.

Subsequently, Phase 1 trials for various cancer indications and HepC  have been completed.
A co-infection trial for HepC and HIV in phase 1 is on going and interim results should be reported soon.
Phase ll cancer trials for various indications have commenced and of course a simple search of clinicaltrials .gov can confirm.

My point here is to show that the science has developed to the point of Phase ll status. Considering the unique moa of this new paradigm, specifically the fact that the antibody attaches to exposed ps and does not go directly after the virus or cancer indication, potentially, gives the antibody broad therapeutic properties. Of course the trials in vivo have to be completed to prove total effectiveness and safety , but results thus far have shown top line safety data and some efficacy.

CHAVI has made Dr. Thope's lab part of their global initiative to find a cure and vaccine for HIV .
 I believe they are using another form of Bavi (2g12) along with other broadly neutralizing antibodies in their pre-clinical efforts, many of which I have reported in this thread.

 Dr. Barton Haynes, Director of CHAVI, explained how exposed ps shields the virus from the immune system (see patents at beginning of this thread) and how any cure or vaccine will have to address this issue.

With the release of the vaccine research study (the shiv re-challenge study by PA Marx,D Montefiore et al.), I believe we will be hearing from CHAVI fairly soon. I certainly hope so. Who knows, Bavi might qualify for the FDA's fairly new Animal Rule.

I've tried to develop this thread,referencing studies and announcements pertinent to the science as it develops . I fully understand the caveats concerning the science and qualified my statements in previous posts addressing that issue (ie: if the science proves itself as it has done in pre-clinicals). What I don't want to see here is mis-information touted as fact without references.

 Bavi , in and of itself might not be the answer. Maybe a second generation Bavi will have to be developed. But I believe that this approach is the most promising and could possibly be the HOLY GRAIL.

I'll be following this science until proven otherwise.

veritas
Title: Re: Could this be the holy grail ?
Post by: Ann on January 16, 2009, 08:02:39 am
Veritas,

Have you ever heard of paragraphs? I can't get through your massive blocks of text without going cross-eyed.

Ann
Title: Re: Could this be the holy grail ?
Post by: veritas on January 16, 2009, 08:13:52 am

Ann,

Thankyou for correcting my sentence structure. I'll have to watch that in the future.

What did you think of the content?


veritas





























Title: Re: Could this be the holy grail ?
Post by: Ann on January 16, 2009, 08:21:42 am
Veritas,

That's just the point. I can't READ the content due to crossed-eyes.

Next time you're in research mode, why not research "writing for the internet"? Most guides will tell you to break your text up into paragraphs of five or so sentences to make what you write readable!

Ann
Title: Re: Could this be the holy grail ?
Post by: veritas on January 16, 2009, 09:01:04 am

Ann,

I'll have to checkout those guidelines.

In the meantime, I'd sure like to hear your comments about the post's content since you are a moderator. Can you try to get through the post? If not, I won't pursue it.

veritas
Title: Re: Could this be the holy grail ?
Post by: Ann on January 16, 2009, 09:16:10 am
Veritas,

I can't. I already have a headache. You can still edit, why don't you go fix it so it can be read?

Ann
Title: Re: Could this be the holy grail ?
Post by: veritas on January 16, 2009, 09:45:38 am

Ann,

Just for you the post is modified.

Anxiously awaiting your remarks!


veritas
Title: Re: Could this be the holy grail ?
Post by: veritas on January 16, 2009, 10:03:14 am

More anti-ps research:




CONCLUSIONS
“The AIDS Vaccine 2008 conference was primarily focused on basic research. Much of this was dealing with broadly-neutralizing anti-HIV antibodies. The few, rare, known familiar suspects: 2F5, 2G12, b12, were the subject of hundreds of experiments presented at the conference. It seemed that "the way forward" was thought to be via insights into these promising antibodies, 2 of which bind a lipid and the virus, and one of which (b12) binds a sugar that coats a viral protein. According to other interesting data presented at the conference, the antibody b12 is apparently the most potent of the three. Along comes Duke University's researcher [Dr. Tony Moody], and presents data from CHAVI 005 experiments, showing that they've got an antibody [PPHM-Duke Collab. mab ‘PGN632’] which only binds a lipid. This particularly potent antibody is orders of magnitude more potent than even b12, and in subtype-C HIV viruses, ( a very common subtype), the anti-lipid antibody was over 1000 times more potent than b12, 2F5, and 2G12. If that is not enough of a surprise to the field, to continue the out-of-the-box theme, it turns out that this unprecedented incredibly powerful antibody works by sticking to a lipid on uninfected T cells, causes an increase in the beta chemokines that block the CCR5 receptor, which prevent HIV from entering a cell in the first place.”

From ‘CAPE TOWN WRAP-UP’ on JBM’s Anti-PS Blog…
“Anti-Lipid Antibodies make their debut at the Cape Town, South Africa AIDS Vaccine 2008 Conference
Title: Re: Could this be the holy grail ?
Post by: bimazek on January 16, 2009, 07:34:08 pm
Big breakthru by Scientists Create Technique to Screen Antibody Libraries against Large Antigen Libraries
and the did it first with HIV.

Here is the good news, imagine you have every key for every lock in the usa in a pile, perhaps 800 million different keys.   the keys are antibodies, now imagine you have one keyhole, and you have to go thru each one individually and figure out if it will fit in the keyhole

well now scientists can do this screening for the key and keyhole for giant liibraries of keys not one at a time basically

this is a great advance because now the monoclonal antibodies which have a better bio activity and profile and lower toxic profile, cause they are fully human  monoclonal antibodies

can be screen in bulk to see what disease key holes they fit

this part i am extrapolating and anyone who is a brilliant molecular biochem genetisist please refine my concepts (they cant be wrong btw lol) anyway


this part i am extrapolating and anyone who is a brilliant molecular biochem genetisist please refine my concept--  every HIV drug has a target which is a keyhole so to speak, on an hiv enzyme, and the drugs that we use are chemicals that have a shape that fit into the keyholes in hiv, well the problem with a chemical key -- a drug -- is the key also has shapes and parts that do not fit into the keyhole but are part of the shape of the handle of the key,  and this part also has interaction with the delicate biological molecules and dna that make you you, so that is a toxic side effect of a chemical drug

where as a  fully human  monoclonal antibody has a shape that fits into the hiv keyhole, turning enzyme off, but also the handle end of the key --- of the fully human  monoclonal antibody has a fully human  shape it  has been genetically engineered to be so perfectly shaped that mostly it does not interact with with human body that is not the keyhole of hiv enzyme for example

remember also that all fully human  monoclonal antibody shapes as well as all chemical drug molecular shapes have electro magnetic charged regions on them so they have a natural attraction to the key shape for the keyhole shape by electro magnetic attraction

kind of like your favorite dildo just fits right in  lol

anyway

now scientists as of today can screen thousands if not tens of thousands of these fully human  monoclonal antibody shapes to see which fit into which parts of disease molecules enzymes etc.

this will be a great leap forward for Antibody Libraries     Antigen Libraries    fully human  monoclonal antibody medicinal treatments for many many disease targets, and also remember

a year ago harvard discovered all 273 target enzymes in human cell that hiv high jacks so that is some great targets

remember also that it is the tools of science like this that sometimes create the biggest leaps forward

i am so good at making analogies and explaining science that it sometimes scares me, ten point bonus question, what writers did i read extensively in science education in my formative years that influenced my truth of knowing that complex science can be explained in simple language to layman without loosing the deep insights....

i will give you a hint... the technique below as well as the writer love and use robots

Create Technique to Screen Antibody Libraries against Large Antigen Libraries

Jan 14 2009, 10:36 AM EST

Scientists Create Technique to Screen Antibody Libraries against Large Antigen Libraries
GEN News Highlights

Investigators at the Scripps Research Institute report that they have developed a technique that enables antibody screening against massive libraries of targets.

Past attempts to instead screen antibody libraries against antigen libraries have been stymied by a variety of technical challenges. A key aspect to the success of the new technique is the use of yeast cells to display the antibodies for screening and phages for the antigens, the researchers explain. Each display was labeled by a different colored fluorescent protein. Screen results were then determined using flow cytometry. Bound pairs are then filtered out of the mix for identification of the antibody and antigen involved.

“It took us a while to get to the right conditions,” remarks Diana Bowley, Ph.D., a Scripps Research staff scientist, “but now that we have, it’s quite easy to visualize and isolate the antibody-antigen pairs.”

The team focused its initial experiments on a known interaction between a specific antibody and a fragment of a protein found on the outside of HIV particles. The group worked with some 10 million antibodies, but the library was weighted to include a known antibody. The antigen library was of similar size and comparably weighted to include the known HIV antigen. The weighting guaranteed the existence of an antibody-antigen pair, which in turn allowed the group to tweak its initial concept until it could identify pairings at the expected rate.

“Many scientists have long recognized that efficient and sufficient access to the libraries demands an effective technique for also screening target antigens by the millions,” notes Richard A. Lerner, M.D., Scripps Research president. “This work now makes that possible.”

The work is reported in this week’s early edition of Proceedings of the National Academies of Science.  http://www.genengnews.com/news/bnitem.aspx?name=48115389&source=genwire
Title: Re: Could this be the holy grail ?
Post by: Ann on January 17, 2009, 07:06:23 am
Veritas,

I think that just because something has entered phase two trials doesn't mean it's not going to run up against major obstacles. Like David mentioned, we've seen too many promising treatments come to nothing to get overly excited about this just yet. This research, despite the time already spent on it, truly is still in its infancy.

Ann
Title: Re: Could this be the holy grail ?
Post by: veritas on January 17, 2009, 10:00:47 am
Veritas,

I think that just because something has entered phase two trials doesn't mean it's not going to run up against major obstacles. Like David mentioned, we've seen too many promising treatments come to nothing to get overly excited about this just yet. This research, despite the time already spent on it, truly is still in its infancy.

Ann


Ann,
I'm fully aware that the therapy could possibly run into obstacles as the trials go on, however, the number of patients dosed to date, covering various viral and cancer targets plus re-dosing , number greater than 100. Not a significant number when comparing to Phase lll  trials where there could be thousands. However, in all patients dosed to date there have been no adverse effects and some of the cancer patients in the phase 1 trials were terminal (see clinical trials and company reports).

It's true that we have been disappointed many times in the past but all those therapeutic disappointments had one thing in common. They went after the virus directly. The broad therapeutic value of anti-ps is unique, a new paradigm, that links to a primary function of the host cell without causing cellular stress to those cells where ps has not flipped. The virus seems to be too stealthy for such a direct approach. A Trojan Horse (Bavi) is needed to attach to the virus to alert a strong Spartan  army ( your immune system) to get rid of the invader. That being said, I realize the clinical trials must be completed and time will tell the value of the therapy.

The most respected researchers in the country have embraced anti-ps for both viral and cancer indications. Their findings to date have been positive (see the 40 references inthe post  hiv - anti-ps breakthrough). If someone can find a negative peer review please post. I have not been able to find any.

I guess the definition of infancy is fluid. I don't happen to agree but the point is really not worth debating.

As far as this thread is concerned, no one has to get excited about this research if they don't want to. However, this is the Research News and Studies Forum and I felt that this research would be an appropriate addition.If my excitement for this therapy comes through, it's because I believe that this could be the Holy Grail. No one else need believe it.

veritas







Title: Re: Could this be the holy grail ?
Post by: J220 on January 18, 2009, 01:29:49 am
I feel very optimistic about bavituximab, but mainly because of the novel method of action. I'll wait for further clinical results before I take it to the next level of confidence. It's possible, after all, that it could work. And wouldn't that be something...

I can say this however, last week I bought 100 shares of Peregrine stock (PPHM), just in case lol
Title: Re: Could this be the holy grail ?
Post by: veritas on January 18, 2009, 04:21:22 am

J220,

Barvituximab(the one in clinical trials) is the first anti-ps mab developed. Another name for it is the 3g4 antibody. CHAVI is working with second generation anti-ps antibodies that are stronger. That being said I am anxiously awaiting interim results on the co-infection trial of Hep c/hiv for efficacy. Those results will give us a good indication as to efficacy beyond pre-clinical for HIV. My hope is that the mabs that CHAVI is working on do the trick ( no pun intended). lol

veritas
Title: Re: Could this be the holy grail ?
Post by: bimazek on January 18, 2009, 06:01:53 pm
more info

To prove the concept, the group focused its initial experiments on a known interaction between a specific antibody and a fragment of a protein found on the outside of HIV particles. The group worked with some 10 million antibodies, but the library was weighted to include a known antibody. The antigen library was of similar size and comparably weighted to include the known HIV antigen. The weighting guaranteed the existence of an antibody-antigen pair, which in turn allowed the group to tweak its initial concept until it could identify pairings at the expected rate.

http://www.sciencedaily.com/releases/2009/01/090115164611.htm

New Technique To Tap Full Potential Of Antibody Libraries Developed
ScienceDaily (Jan. 15, 2009) — In hopes of more fully tapping the libraries' potential, a group of Scripps Research Institute scientists, led by Scripps Research President Richard A. Lerner, M.D., has for the first time developed a new screening technique that enables antibody screening against equally massive libraries of targets. This technique makes it possible to accelerate searches for new treatments against cancer and other diseases.
See also:
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The work was recently reported in the Early Edition of the journal Proceedings of the National Academies of Science (PNAS).
The immune system produces antibodies to immobilize invaders, such as bacteria and viruses, by attaching to proteins referred to as antigens on those invaders. For many years, researchers have been producing huge collections of synthetic antibodies that collectively dwarf the number of antibodies humans produce naturally. These resources are a synthetic immune system with almost limitless potential, but existing techniques have only enabled screening the millions upon millions of available antibodies against handfuls of antigens.
"Many scientists have long recognized that efficient and sufficient access to the libraries demands an effective technique for also screening target antigens by the millions," said Lerner. "This work now makes that possible."
Traditional antibody research has involved developing systems in which the antibodies to be tested are incorporated into yeast cells, bacterial viruses known as phages, or some other form of "display" for testing against a target antigen protein. Past attempts to instead screen antibody libraries against antigen libraries have been stymied by a variety of technical challenges.
A key aspect to the success of the Lerner group's technique is using yeast cells to display the antibodies for screening, while using phages for the antigens, with each display labeled by a different colored fluorescent protein.
Screen results are determined using flow cytometry, a technique that allows the researchers to examine images of the yeast cells and phage particles and manipulate them. Using the differing displays means that antibody-antigen pairs that bind can be easily identified, because they show both fluorescent dye tag colors. Bound pairs are then filtered out of the mix for identification of the antibody and antigen involved, which requires genetic sequencing.
"It took us a while to get to the right conditions," says Diana Bowley, Ph.D., a Scripps Research staff scientist and the paper's first author with Teresa Jones, a Scripps Research scientific associate, "but now that we have, it's quite easy to visualize and isolate the antibody-antigen pairs."
To prove the concept, the group focused its initial experiments on a known interaction between a specific antibody and a fragment of a protein found on the outside of HIV particles. The group worked with some 10 million antibodies, but the library was weighted to include a known antibody. The antigen library was of similar size and comparably weighted to include the known HIV antigen. The weighting guaranteed the existence of an antibody-antigen pair, which in turn allowed the group to tweak its initial concept until it could identify pairings at the expected rate.
The group was able to successfully identify the expected pairings, proving the new technique's potential to enable screening of large antibody and antigen libraries. "We're still deciding where to take it next," says Bowley. One likely direction would be to work with a broad group of cancer proteins, which should identify antibodies with potential as new cancer treatments.
In addition to Bowley, Jones, and Lerner, Scripps Research Professor Dennis Burton was an author of the paper, titled "Libraries against libraries for combinatorial selection of replicating antigen-antibody pairs."
This research was supported by The Scripps Research Institute, the Skaggs Institute for Chemical Biology, and Pfizer Inc.
Title: Re: Could this be the holy grail ?
Post by: veritas on February 04, 2009, 08:26:35 am

Anti-ps looking good in lung cancer. the moa is the same for virals:

http://finance.yahoo.com/news/Peregrine-Pharmaceuticals-prnews-14247914.html


Can't wait for interim results of HepC/hiv trial!
Title: Re: Could this be the holy grail ?
Post by: veritas on February 04, 2009, 08:56:01 am

more info:


Peregrine Pharmaceuticals has issued a press release with interim data from their phase II NSCLC clinical trial. The Peregrine trial is using their anti-lipid antibody "Bavituximab" which targets exposed phosphatidylserine (PS) in combination with carboplatin and paclitaxel. The Peregrine trial was apparently designed to go head-to-head with the phase II trial of what is currently the standard of care for non small cell lung cancer, (Avastin with carboplatin and paclitaxel). The data released today shows Bavituximab achieving a higher percentage of responses than current SOC.

Title: Re: Could this be the holy grail ?
Post by: veritas on February 08, 2009, 05:10:05 am

More broadly neutralizing data with respect to an HIV vaccine:


http://www.ncbi.nlm.nih.gov/pubmed/19193787?dopt=Abstract
Title: Re: Could this be the holy grail ?
Post by: veritas on February 08, 2009, 05:34:38 am

More studies ------ X4 vs R5  for vaccine design:


Selective replication of X4 and R5/X4 HIV-1 during the in vitro primary CD4+ T cell response
The ability of R5, X4, and R5/X4 isolates of HIV-1 to replicate in CD4+ T cells during the primary in vitro immune response was determined using a system developed by our group to evaluate the synthesis of anti-viral CCR5 ligands [18], the effects of adjuvants on antigen presentation [19]–[21], and the responses to HIV-1 vaccine candidates [22]. Cultures were initiated and infected with the HIV-1 isolates shown in Figure 1a as described in Materials and Methods. As shown in Figure 1a, five of the six X4 and R5/X4 viruses replicated by day 8 of the culture period. The R5/X4 virus HIV-189.6 replicated poorly, if at all. By contrast, none of the four R5 viruses replicated early in the culture period with only HIV-1SF162 showing a modest increase in p24 by day 11. Since the differences in replication appeared to be greatest during the first 11 days of culture, we compared the day 8 median p24 concentrations of the three groups for statistical significance using Student's t-test. As shown in Figure 1b, the differences between the R5 group and either the X4 or X4/R5 groups were statistically significant (p = 0.02) for X4 viruses, p≤0.05 for X4/R5 viruses). These data show that X4 and X4/R5 viruses selectively replicate during the antigen driven primary CD4+ T cell response in vitro with little or no replication of R5 viruses under these experimental conditions. This conclusion was confirmed in subsequent experiments by analysis of intracellular p24.

http://www.plosone.org/article/info:doi%2F10.1371%2Fjournal.pone.0003481

The above link is a long read however, the full study shows that both  are able to be controlled in potential vaccine design.

veritas
Title: Re: Could this be the holy grail ?
Post by: veritas on February 11, 2009, 08:14:21 am

Anti-ps looking good in breast cancer for interim phase 2. Same moa in viral as in cancer:


http://finance.yahoo.com/news/Peregrine-Pharmaceuticals-prnews-14321025.html


Anxiously awaiting interim results for HepC/Hiv co-infection trial. CHAVI has anti-ps mabs that are a lot more potent than Bavi for their vaccine initiative.

veritas
Title: Re: Could this be the holy grail ?
Post by: veritas on February 11, 2009, 08:40:58 am

I wonder what is going to be discussed at this syposium?


http://www.keystonesymposia.org/Meetings/ViewMeetings.cfm?MeetingID=990

Read the entire program for the answer.


veritas
Title: Re: Could this be the holy grail ?
Post by: veritas on February 11, 2009, 09:25:26 am

More info about the Bavi trial:



Anti-PS (Bavituximab)

Phase II Breast Cancer Data:


* seven out of fourteen responses
* including one complete response
* in locally advanced or metastatic breast cancer patients

How early is it?...

* these results after two 28-day treatment cycles
* patients will receive up to six treatment cycles


"Bavituximab Has Now Produced Positive Early Results in All Three Ongoing Phase II Combination Therapy Cancer Trials"

veritas
Title: Re: Could this be the holy grail ?
Post by: veritas on February 16, 2009, 04:19:24 pm

This study is still enrolling as of 12/08:


http://clinicaltrials.gov/ct/show/NCT00503347


co-infection trial HepC/hiv with Bavituximab (anti-ps).
Title: Re: Could this be the holy grail ?
Post by: veritas on February 18, 2009, 09:47:23 am

Chavi determining how quickly a vaccine response will have to be:


Initial B cell Responses
Show Ineffective Control of
Viremia in Acute HIV
Infection
Dr. Georgia Tomaras of Duke
University and colleagues found that the
earliest B cell immune responses to HIV
are ineffective at controlling viral
replication in the earliest stages of
infection. Their study of the earliest
antibody responses in acute HIV
infection was published in the December
issue of the Journal of Virology.
One of CHAVI’s goals is to elucidate
the eclipse phase of HIV infection when
a vaccine has the best chance to clear or
neutralize the virus. This “window of
opportunity” is the period of time from
the point of transmission to the
establishment of the latent pool of
infection. It is approximately 10 days
from transmission when virus can be
detected in blood plasma, but can range
between 7-21 days after transmission. In
this study, Tomaras and colleagues
wanted to determine the antibodies that
respond first to HIV, the time points
when they appear in relation to viral
load, and how well they control viral
replication.
Studying samples from plasma donors
who donated every three days and who
became newly infected with HIV, the
team was able to view the earliest
antibody responses before, during and
after plasma viral load ramp-up in acute
HIV infection. The team found that the
first response came 8 days after
transmission in the form of immune
complexes containing either the antibody
Immunoglobulin G (IgG) or M (IgM)
that bound to virions. The antibodies,
anti-Env IgG and anti-Env IgM, were
detected in plasma 13 days after
transmission. Both IgG and IgM
targeted the glycoprotein, gp41, on the
outer coat of the virus.
Using mathematical modeling, the
team determined whether the initial gp41
antibody response was able to control
viral replication. They found no
relationship between the strength of the
anti-gp41 antibody response and a
decrease in viral load indicating that the
initial antibody response had little
impact on control of viremia.
The team concluded from this study
that the potential window of opportunity
for a vaccine to work appears very short.
They are currently taking a closer look at
the immune complexes that first
appeared 8 days after transmission to see
if they may be manipulated to boost
immunity. A suggested hypothesis is
that a primary boost vaccine would need
to induce antibodies prior to infection
followed by a rapid and robust secondary
response within the first week after
transmission that would be capable of
clearing or neutralizing the virus.
Title: Re: Could this be the holy grail ?
Post by: veritas on February 23, 2009, 01:12:04 pm

Duke finds potent anti -ps antibody for hiv:

http://insciences.org/article.php?article_id=2626

Successfully neutralizes over 80% of transmitted HIV viruses.
Title: Re: Could this be the holy grail ?
Post by: veritas on February 25, 2009, 05:19:19 am

Back-up research on 2F5 and 4E10 mab:


http://www.ncbi.nlm.nih.gov/pubmed/19193787?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

Duke has mabs stronger than the above. Anti-ps is becoming more viable !

veritas
Title: Re: Could this be the holy grail ?
Post by: veritas on February 25, 2009, 09:49:41 am

For those following this thread, this link is worth repeating. Take particular interest in the neutralizing antibody section and notice the potency of IS4 antibody. This antibody seems to have the potency necessary for therapeutic application as suggested in the world patent application at the very beginning of this thread:

http://www.hivvaccineenterprise.org/conference/archive/2008/Presentations/Thursday/Rapporteurs/1250%20R%20Pantophlet.pdf

The above link is not an easy read.
Title: Re: Could this be the holy grail ?
Post by: veritas on February 25, 2009, 11:37:20 am

The most potent mab is PGN632, which neutralized 7/7 hiv clades B and C isolates:


Oct. 14, 2008, Oral Abstracts 03: “Neutralizing Antibodies & Immune Escape”
#OA03-06 ”Anti-lipid Human Monoclonal Antibodies Inhibit HIV-1 Infection of PBMC by Binding to Host Cells”
TONY MOODY [Dir., Laboratory of B cell Immunology, Duke Univ. MC]
MA Moody 1, MK Plonk 1, L Fuller 1, H Liao 1, S Xia 1, MS Drinker 1, TC Gurley 1, RM Scearce 1, GD Tomaras 1, C Chang 2, S King 2, A Kavlie 3, PE Thorpe 4, SM Alam 1, PP Chen 5, DC Montefiori 6, BF Haynes 1
1 Duke University Medical Center, Durham, NC
2 Peregrine Pharmaceuticals, Tustin, CA
3 Affitech AS, Oslo, N-0349, Norway
4 University of Texas Southwestern Medical Center, Dallas, TX
5 UCLA School of Medicine, Los Angeles, CA
6 Dept. of Surgery, Duke University Medical Center, Durham, NC
BACKGROUND:
HIV-1-infected or vaccinated humans rarely make broadly-reactive neutralizing antibodies. Some antibodies against conserved Env epitopes share similarities with autoantibodies; one hypothesis is such antibodies are downregulated by immune tolerance. The observation that AIDS may be rare in primary autoimmune disease patients (1) prompted the hypothesis that autoimmune disease patients with defective tolerance mechanisms may make antibodies that in some manner protect against HIV-1 infection. Methods: We studied a panel of human anti-lipid mAbs from autoimmune disease patients and healthy controls. Mabs IS4, CL1, P1, and PGN632 bind cardiolipin and phosphatidylserine independent of b2-glycoprotein I; mAbs B1, B2, PGN634, and PGN635 require b2-glycoprotein I for lipid binding. Inhibition of HIV-1 infection was studied using HIV-1 Env pseudoviruses in TZM/bl cells and using whole virus assays in peripheral blood mononuclear cells (PBMC). MAb interaction with Env, lipids, and cells was determined by surface plasmon resonance (SPR), flow cytometry, and fluorescent microscopy.
RESULTS:
No mAbs bound HIV-1 wild-type Envs by SPR and none significantly neutralized HIV-1 primary isolate pseudoviruses in the TZM/bl assay. In PBMC, b2-glycoprotein I-dependent mAbs minimally inhibited infection. In contrast, b2-glycoprotein I-independent anti-lipid mAbs (PGN632, P1, IS4, CL1) inhibited HIV-1 primary isolate infection of PBMC (IC80s<0.02 to 45 mg/ mL). The most potent mAb PGN632 inhibited 7/7 B & C clade HIV-1 isolates (IC80s<0.02-0.16 mg/mL) and SHIV-SP162P3 (IC80 0.06 mg/mL). Cell preincubation and virus capture studies showed the mAbs acted at host cell surfaces to inhibit HIV-1 infection. Immunofluorescence of CD4þ T cells showed the mAbs bound to lipid rafts.
CONCLUSION:
Anti-lipid human mAbs inhibit HIV-1 infection in vitro in PBMC likely by binding CD4þ T cell lipid rafts. Testing these mAbs in passive therapy trials in vivo in non-human primates will be important to determine their protective effect. Nonpathogenic anti-lipid antibodies may provide a target for HIV-1 vaccine development.
PAGE 57, #OA03-06: http://www.hivvaccineenterprise.org/_dwn/forms/Final%20Abstract%20Book.pdf
*end*

Title: Re: Could this be the holy grail ?
Post by: veritas on February 27, 2009, 09:29:17 am

Since this thread is getting so long, thought I would post this press release again which reviews anti-ps as a therapeutic and possible vaccine for many viral indications:


http://www.zampbioworld.org/bionews/index.php/2008/11/25/11813
Title: Re: Could this be the holy grail ?
Post by: veritas on February 28, 2009, 03:31:22 pm

What is allowing HIV to escape the immune system? Could it be exposed ps on infected cells?

http://www.sciencedaily.com/releases/2009/02/090227150549.htm

Sounds like a viable therapy should go after a part of the infected cell that cannot mutate. Anti-ps anyone?

veritas
Title: Re: Could this be the holy grail ?
Post by: veritas on March 02, 2009, 05:40:06 am

What else can anti-ps do?  Arsenic anyone?


http://engg-medi.blogspot.com/

Sunday, March 1, 2009

Using arsenic to detect cancers?
An international team led by Texan researchers is using arsenic as a powerful tumor imaging agent. In fact, they are using a drug called bavituximab, 'an antibody that homes in on a specific molecular target on the blood vessels that feed tumors.' By linking this drug to very small doses of arsenic -- about one-millionth of what could be considered as poison -- they think it could allow physicians to detect hard-to-find tumors in a near future. The combination has already successfully tested with rats affected by prostate tumors. And it could soon be used on on humans to image breast tumors. But read more...
The Bavituximab drug is a monoclonal antibody analog which is used to potentially treat cancers and viral infections. (Credit: Wikipedia) It has been licensed by Peregrine Pharmaceuticals, Inc. from UT Southwestern Medical Center. As you can see above on the left, Bavituximab can be used as an anti-cancer drug, "Bavituximab binding to the tumor blood vessel cells alerts the body's immune system to attack the tumor and its blood supply" (Credit: Peregrine). But it also can be used as an anti-viral drug as you can see on the right. "After binding to these infected cells, the drug alerts the body's immune system to attack the infected cells" (Credit: Peregrine).
Binding tiny doses of arsenic to bavituximab is a project led by Dr. Philip Thorpe, professor of pharmacology at the University of Texas Southwestern Medical Center, and by Dr. Ralph Mason, professor of radiology and director of the UT Southwestern Cancer Imaging Program.
So why did these scientists decide to hire arsenic for help? The first reason is because "arsenic-labeled bavituximab appears to be safe." The second one is because it works. "In the study, Dr. Thorpe and his colleagues injected radioarsenic-labeled bavituximab into rats with prostate tumors. When the bavituximab bound to its target on the the tumor blood vessels, the tag-along arsenic created a 'hot spot' that researchers then imaged using positron emission tomography methods. The radioactivity levels produced by the arsenic are comparable to those used in standard, routine imaging procedures in humans. The technique allowed them to locate and capture unusually clear images of the tumors. They also discovered that there was little or no detectable uptake of bavituximab by normal organs, including the liver, a common site where drugs become entrapped."
Here is a quote from Thorpe. "We hope to use this technique to detect early tumor deposits that are not visible using other imaging techniques. The images we obtain are so clear that we may be able to see secondary tumors that have spread from the original tumor mass and lodged in distant organs."
This research work is scheduled to appear in the March 1, 2008 issue of Clinical Cancer Research under the name "Vascular Imaging of Solid Tumors in Rats with a Radioactive Arsenic-Labeled Antibody that Binds Exposed Phosphatidylserine." Unfortunately, the journal site gives access to its February 15, 2008 issue and gives a preview of its March 15, 2008 issue, but doesn't show anything about its March 1, 2008 issue.
But for more information, you can read a March 3, 2008 news release from Peregrine Pharmaceuticals, which states that Bavituximab can successfully target tumor blood vessels. Here is a quote. "In the study, researchers administered radiolabeled bavituximab to rats with prostate tumors and then conducted molecular imaging studies of the rats over the next several days. The results showed that radiolabeled bavituximab localized to the tumor blood vessels with great specificity. In these subjects, 22 times as much bavituximab localized to the tumor compared to the liver when measured 72 hours post-injection. The study further showed no specific localization of bavituximab to blood or other tissues including the heart, kidney, intestine, muscle, bone and brain. The tumor blood vessel-selective targeting observed in vivo in the study was confirmed by further bio-distribution analyses and by histology studies."
So are you ready for arsenic? Drop me a note if you think it's a good -- or bad -- idea.
Sources: University of Texas Southwestern Medical Center news release, March 1, 2008; and various websites
You'll find related stories by following the links below.
Chemistry
Future
Medicine
Physics
Science
Title: Re: Could this be the holy grail ?
Post by: veritas on March 03, 2009, 04:00:19 am
PS explained:
FYI: Antiviral Drugs: Exposed target for broad-spectrum antivirals

http://www.nature.com/nrd/journal/v8/n1/full/nrd2788.html
Nature Reviews Drug Discovery 8, 19 (January 2009) | doi:10.1038/nrd2788
Man Tsuey Tse

Phosphatidylserine, the most abundant anionic phospholipid of the plasma membrane, has been used as a target to develop a novel broad-spectrum antiviral agent called bavituximab. Strikingly, bavituximab was able to cure overt disease in guinea-pigs infected with a potentially lethal dose of Pichinde virus, a model of Lassa fever virus.

Writing in Nature Medicine, Thorpe and colleagues proposed that the effects of a wide range of viruses on host cells could lead to normally intracellular anionic phospholipids being exposed on the surface of infected cells. To test this hypothesis, they used bavituximab — a chimeric antibody that binds to complexes of the phosphatidylserine-binding plasma protein 2-glycoprotein 1 and anionic phospholipids. These experiments showed that infection of mouse cells by Pichinde virus led to phosphatidylserine exposure, and that bavituximab binds to virus-infected cells and infectious virions.

Treatment of guinea-pigs infected with a normally lethal dose of Pichinde virus with bavituximab 6–7 days after infection led to 50% of the animals surviving, and clearance of the virus was observed by day 135. In addition, combination of bavituximab with ribavirin (the current drug of choice for treating Lassa fever) had an additive effect.

The authors also provided evidence for two mechanisms that seem to underlie these effects. First, bavituximab treatment clears infectious virus from the bloodstream. Second, it induces antibody-dependent cellular cytotoxicity of virus-infected cells. As the authors propose, it seems that phosphatidylserine on virions and infected cells might enable viruses to evade immune recognition and dampen inflammatory responses, and that bavituximab interferes with this 'masking' process.


Finally, the authors explored phosphatidylserine exposure in other viral infections. Exposure was also observed in cells infected with influenza virus, vaccinia, vesicular stomatitis virus and mouse cytomegalovirus (CMV). This indicates that this process is a common feature of enveloped viruses; exposure could also extend to non-enveloped viruses. Furthermore, tests in mice infected with an almost lethal dose of CMV showed that all treated mice survived, in contrast to untreated mice, of which only 25% were alive after 96 days.

In both animal models, bavituximab was well tolerated, and no toxicity was observed histologically. Therefore, targeting phosphatidylserine shows promise as an antiviral strategy. In addition, as phosphatidylserine is a host-derived target, the development of resistance could be limited. Clinical trials of bavituximab are currently underway in patients with hepatitis C co-infected with HIV.

***********

Inside-out antivirals
Phosphatidylserine is actively maintained in the inner leaflet of the membranes of healthy cells, but 'flips' and becomes exposed on the cell's exterior during apoptosis. Having first shown that this phenomenon is triggered by infection with a range of viruses in vitro, Soares et al. exploit the loss of asymmetry in the membranes of virally infected cells and enveloped virions by demonstrating the potential of aminophospholipids as antiviral targets. Inspired by studies suggesting the immunosuppressive and anti-inflammatory potential of exposed phosphatidylserine, they show that a chimeric antibody (bavituximab) against complexes comprising a phosphatidylserine-binding plasma protein and anionic phospholipids enhances the robustness of the immune response to viral infection. Treatment with bavituximab not only cured guinea pigs lethally infected with Pichinde virus (a model for Lassa fever virus, a potential bioterrorism agent), but also rescued mice with lethal cytomegalovirus infections. The antiviral effects can primarily be attributed to direct virus clearance from the bloodstream and antibody-dependent cellular cytotoxicity. Bavituximab treatment appears to be well tolerated and augments the antiviral effect of ribavirin, the drug of choice for treating Lassa fever. (Nat. Med. 14, 1357–1362)



References and links
ORIGINAL RESEARCH PAPER
Soares, M. M., King, S. W. & Thorpe, P. E. Targeting inside-out phosphatidylserine as a therapeutic strategy for viral diseases. Nature Med. 23 Nov 2008 (doi: 10.1038/nm.1885)




 
Title: Re: Could this be the holy grail ?
Post by: carpediem98 on March 12, 2009, 02:23:20 pm
Great work in this thread, Veritas!

I referenced you and the research you've highlighted in a DailyKos thread.  It gave OTHERS hope, as well.  :) 

http://www.dailykos.com/story/2009/3/7/141053/0717/16/705776 (http://www.dailykos.com/story/2009/3/7/141053/0717/16/705776)

Keep spreading the hope - and I hope our optimism is well-placed!
Title: Re: Could this be the holy grail ?
Post by: veritas on March 12, 2009, 05:16:21 pm

carpediem98,

I started this thread with the intention of giving others hope. If, by referencing this thread, some of your readers were the recipients of that hope then I feel as though I've been successful.

I know anti-ps is a new paradigm in the fight against HIV (and other diseases) and I also understand that being a new paradigm, its value will have to be tested vigorously to prove its merit. However ,what i find fascinating about this therapy is that I have not found any negative papers with respect to this research.
Also. peer review has thus far reinforced Dr. Thorpe's research. Early clinical trials seem to be leaning in that direction also (especially with respect to cancer).

My only complaint is the seemingly snail's pace with respect to the anti viral. Alas, you can't rush science!
 
I will be following this research to its conclusion. Please feel free to reference this thread if you find it has merit.

veritas
Title: Re: Could this be the holy grail ?
Post by: veritas on March 14, 2009, 05:09:38 am

Does anti-ps aid in the production of dendritic cells and Il2s ?  It looks that way!



2009 AACR Annual Meeting
April 18-22, 2009
Denver, CO


  Print this Page for Your Records  Close Window 

Abstract Number: 2407
Session Title: Immune Modulating Antibodies and Lymphocyte Transfer
Presentation Title: A novel anti-phosphatidylserine antibody that promotes dendritic cell maturation
Presentation Start/End Time: Monday, Apr 20, 2009, 1:00 PM - 5:00 PM
Location: Hall B-F, Poster Section 16
Poster Section: 16
Poster Board Number: 1
Author Block: Xianming Huang, Dan Ye, Philip Thorpe, Anita Kavlie. UT Southwestern Medical Ctr., Dallas, TX, Affitech AS, Oslo, Norway
11.31 is a fully human anti-phosphatidylserine (PS) antibody that binds to PS directly, as determined by ELISA and by cell staining. In the present study, the effects of 11.31 on bone marrow-derived immature dendritic cells were examined. Bone marrow monocytes were harvested from the femur and tibia of BALB/c mice. Immature dendritic cells were derived by growing bone marrow monocytes in the presence of mouse GM-CSF (20 ng/ml) for 7 days, and the medium replaced with fresh medium containing GM-CSF every other day. Immature dendritic cells were then harvested and cultured in the presence of 11.31 or control human IgG for 48 hours. Cytokine production in the supernatant was measured by ELISA. Maturation of dendritic cells was examined by FACS analysis. We found that 11.31 significantly increased the expression of maturation markers CD40, CD80, CD86 and MHC II on the surface of dendritic cells. 11.31 also significantly increased production of IL-2, IL-6, TNFα, GM-CSF and MIP-1β by immature dendritic cells. Taken together, our results indicate that 11.31 promotes maturation of dendritic cells. 11.31 has the potential to enhance cancer immunotherapy.
 
Title: Re: Could this be the holy grail ?
Post by: simpleguy on March 15, 2009, 02:11:12 pm
Hi! I'm a 40y hiv+ guy (9 months positive) from Denmark who happened to stumble upon this thread about bavituximab and the science behind using mAbs as a possible therapeutic - Wow! This is very exciting!

One thing that got me a bit worried though, was the thing about the mAbs not neutralizing HIV in a TMZ-bl cell assay. Not being a science person, I didn't really understand what it meant, except I got a feeling of "this doesn't sound very good".

According to the OA03-06 Oral Abstract from the Oct. 2008 AIDS Conference "No mAbs [...] significantly neutralized HIV-1 primary isolate pseudoviruses in the TZM/bl assay". According to the paper in the following link, that can be explained by TMZ-bl cell lines having been "engineered" to have an unusual high concentration of CCR5 on the cell surface[1], compared to the (unengineered) PBMC cells. In other words: a TMZ-bl cell assay doesn't reflect in vivo conditions, whereas PBMC does  :-X (the good thing being that the mAbs neutralized hiv in the PBMC cell assays).

Published August 4, 2006
Increased Efficacy of HIV-1 Neutralization by Antibodies at Low CCR5 Surface Concentration
http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=16904645

There's a lot of stuff about the science of hiv I don't understand. More science-knowlegdeable people on this board are welcome to correct me, if I got something wrong. Anyway .. I really hope this Duke-PPHM-Affitech et. al. research about mAbs will lead to a more bearable life with hiv (a shift away from HAART and side effects).

[1] https://www.aidsreagent.org/reagentdetail.cfm?t=cell_lines&id=119

See also
http://en.wikipedia.org/wiki/PBMC
http://en.wikipedia.org/wiki/HeLa

Title: Re: Could this be the holy grail ?
Post by: veritas on March 15, 2009, 03:53:57 pm

simpleguy,

We are all in the same boat with respect to the understanding of HIV. The science is complicated. If it wasn't complicated the powers that be would have come up with a cure.

I am optimistic about anti-ps therapy because it is a new paradigm in the fight against HIV. We know that trying to attack the virus directly(via HAART) does not and will not eradicate hiv from the body. By attaching to a non-mutateable part of the virus,anti-ps allows our immune system to attack the virus and those cells infected with the virus. The problem is trying to get a strong enough immune response to do the job and that's why I agree with you 100% when you said:

"I really hope this Duke-PPHM-Affitech et. al. research about mAbs will lead to a more bearable life with

hiv (a shift away from HAART and side effects)."

Time will tell. Let's hope it is the holy grail.

veritas

ps: so far, anti-ps is working wonderfully in phase ll cancer trials.



Title: Re: Could this be the holy grail ?
Post by: veritas on March 16, 2009, 08:37:17 am

What do we need for a vaccine? B-cells anyone?

http://www3.niaid.nih.gov/news/newsreleases/2009/hiv_antibodies.htm

And what interacts with B-cells to give them the necessary ability for an adaptive immune response to fight a virus ? Dendritic cells anyone?

http://en.wikipedia.org/wiki/Dendritic_cell

And as we saw in an earlier post, what stimulates the production of Dendritic Cells?

ANTI-PS !!!!!!!!!!

Can we connect the dots?

veritas
Title: Re: Could this be the holy grail ?
Post by: veritas on March 17, 2009, 09:53:39 am

Interesting read even though a bit dated. Bavituximab mentioned using its' former name Tarvacin:

http://www.aapspharmaceutica.com/StudentCenter/SPODCommittee/imagespdfs/Pharmaceutical_Discovery_in_21st_century-GK.pdf
Title: Re: Could this be the holy grail ?
Post by: veritas on March 18, 2009, 05:49:09 am

Update on vaccine design. Take particular notice of the remarks by Barton Haynes of Duke University and how anti-ps should play a major part.... Long read:

http://www.cavd.org/SiteCollectionDocuments/CAVD%20Report_%202006-2008%20In%20Review.pdf


veritas
Title: Re: Could this be the holy grail ?
Post by: veritas on March 19, 2009, 12:54:39 pm

Why anti-ps should work:

 HIV/AIDS
A viral cause of APS has been proposed.[318] HIV infection carries a high frequency of aPL[34,319] but here, too, the aPL in HIV were considered to be of the infection-related type and non-pathogenic. Haynes et al[46] point out that anti-HIV antibodies mounted by most patients fail to neutralize the virus, but a rare few do mount neutralizing responses, and those studied turned out to be polyspecific aCL, similar to the aPL profile seen in lupus (SLE). Indeed, they cite references indicating that SLE patients appear to be protected against contracting HIV, and argue that the general population fails to make such aPL because they have been deleted from the repertoire as self-reactive. In support of their contention, one of the neutralizing anti-HIV they studied was autoreactive with dsDNA, centromere B, histones and other self targets.[46] Relatedly, Zhang et al[320] investigated why most people fail to mount effective immune responses to HIV envelope proteins (Env), and suggested that Env suppresses CD40L expression, which in turn blunts the T cell ability to activate DCs. However, we feel that findings of Zhang et al[320] are consistent with the scenario given by Haynes et al.[46] Specifically, the aPL seen in the context of HIV and other infections may be more than epiphenomena and could offer important clues to immune function.

medscape
Title: Re: Could this be the holy grail ?
Post by: veritas on March 21, 2009, 12:24:22 pm


IN VIVO:

In Vivo gp41 Antibodies Targeting the 2F5 Monoclonal Antibody Epitope Mediate
Human Immunodeficiency Virus Type 1 Neutralization Breadth

Xiaoying Shen,1,2 Robert J. Parks,1,4 David C. Montefiori,1,2 Jennifer L.
Kirchherr,1,4 Brandon F. Keele,6 Julie M. Decker,6 William A. Blattner,5 Feng
Gao,1,4 Kent J. Weinhold,1,2,3 Charles B. Hicks,4 Michael L. Greenberg,2,
Beatrice H. Hahn,6 George M. Shaw,6 Barton F. Haynes,1,3,4 and Georgia D.
Tomaras1,2,3*

Duke Human Vaccine Institute,1 Departments of Surgery,2 Immunology,3 Medicine,
Duke University Medicine Center, Durham, North Carolina 27710,4 Division of
Epidemiology and Prevention, Institute of Human Virology, University of
Maryland, Baltimore, Maryland 21201,5 Department of Medicine, University of
Alabama at Birmingham, Birmingham, Alabama 35294-00246

Received 20 December 2008/ Accepted 27 January 2009

The broadly neutralizing human monoclonal antibodies (MAbs) 2F5 and 4E10, both
targeting the highly conserved human immunodeficiency virus type 1 (HIV-1)
envelope membrane proximal external region (MPER), are among the MAbs with the
broadest heterologous neutralizing activity and are of considerable interest for
HIV-1 vaccine development. We have identified serum antibodies from an
HIV-infected subject that both were broadly neutralizing and specifically
targeted MPER epitopes that overlap the 2F5 epitope. These MPER-specific
antibodies were made 15 to 20 months following transmission and concomitantly
with the development of autoantibodies. Our findings suggest that multiple
events (i.e., genetic predisposition and HIV-1 immune dysregulation) may be
required for induction of broadly reactive gp41 MPER antibodies in natural
infection.


Title: Re: Could this be the holy grail ?
Post by: simpleguy on March 21, 2009, 03:12:04 pm
Illustration, showing the size of an antibody compared to the trimer gp41/gp120 and the 2F5 and 4E10 binding sites on the spike of a hiv virion. http://jvi.asm.org/cgi/content-nw/full/75/22/10892/F10

Fascinating...

Taken from a 2001 study on hiv and antibodies
http://jvi.asm.org/cgi/content/full/75/22/10892
Title: Re: Could this be the holy grail ?
Post by: veritas on March 21, 2009, 03:20:21 pm

Anti - ps and dendritic cells:

http://www.abstractsonline.com/viewer/viewAbstractPrintFriendly.asp?CKey={1DE14776-AF63-4524-91C8-11AB9743EB16}&SKey={B11EE4CC-F5A4-4AC4-841E-EE7ECD227FF2}&MKey={D007B270-E8F6-492D-803B-7582CE7A0988}&AKey={728BCE9C-121B-46B9-A8EE-DC51FDFC6C15}
Title: Re: Could this be the holy grail ?
Post by: veritas on March 21, 2009, 04:05:09 pm
Illustration, showing the size of an antibody compared to the trimer gp41/gp120 and the 2F5 and 4E10 binding sites on the spike of a hiv virion. http://jvi.asm.org/cgi/content-nw/full/75/22/10892/F10

Fascinating...

Taken from a 2001 study on hiv and antibodies
http://jvi.asm.org/cgi/content/full/75/22/10892


Simpleguy,
Your illustration shows how targeted these antibodies are.  Since ps is only exposed on virons, infected cells, and dying cells, side effects, if any, should be minimal. In clinical trials to date, only topline safety data has been reported (see earlier posts). By magnifying the illustration, you can get the full effect of the moa (especially for those of us who need the magnification.)

The work is fascinating !

veritas
Title: Re: Could this be the holy grail ?
Post by: Inchlingblue on March 21, 2009, 05:35:29 pm
Our findings suggest that multiple events (i.e., genetic predisposition and HIV-1 immune dysregulation) may be
required for induction of broadly reactive gp41 MPER antibodies in natural infection.

I'm trying to figure out this sentence in laymen's terms. Any suggestions?
Title: Re: Could this be the holy grail ?
Post by: simpleguy on March 21, 2009, 07:40:38 pm
The theory is that broadly reactive antibodies (able to neutralize different clades and/or mutations of hiv) produced by your own body, probably only takes place in a body with a "twisted" immune system, for example in people suffering from the autoimmune disease Lupus; a disease characterized by the body producing antibodies which stick to healthy tissue and signaling the immune system to attack it. Lupus could be the result of "genetic predisposition".

The antibody "overlapping the 2F5 epitope", isolated from the hiv+ subject, was found at a time where autoimmune antibodies were also present, probably because that person is suffering from an autoimmune disease. Research shows that very few people with autoimmune disease are hiv+, and if they are, their hiv doesn't progress.

gp41 MPER = the spikes on the surface of hiv virus
Lupus: http://en.wikipedia.org/wiki/Systemic_lupus_erythematosus
Title: Re: Could this be the holy grail ?
Post by: Inchlingblue on March 21, 2009, 08:04:49 pm
Thanks, Simpleguy, that clears it up. I "get" it.
Title: Re: Could this be the holy grail ?
Post by: simpleguy on March 21, 2009, 09:11:08 pm
lol ... ;o)

I was quoting from the article that veritas posted (#140)
Title: Re: Could this be the holy grail ?
Post by: veritas on March 25, 2009, 09:46:22 am

More B-cells and hiv:


B cells in HIV infection and disease
Susan Moir1 & Anthony S. Fauci

http://www.nature.com/nri/journal/v9/n4/execsumm/nri2524.html
Nature Reviews Immunology 9, 235-245 (April 2009) | doi:10.1038/nri2524

Summary

HIV infection leads to perturbations of all of the main cell types of the immune system, including B cells. Most B-cell perturbations are associated with indirect effects of ongoing HIV replication, although some perturbations arise regardless of the decrease in viraemia by effective antiretroviral therapy (ART).
Many B-cell defects in HIV infection are associated with alterations in the B-cell subpopulations that circulate in the peripheral blood. Most B cells in healthy individuals comprise resting naive and memory B cells, whereas several minor subpopulations are over-represented in HIV-infected individuals, including immature transitional B cells, exhausted B cells, activated mature B cells and plasmablasts.

In vitro and in vivo studies show that HIV can also interact directly with B cells, although the frequency of these interactions is unlikely to account for the extent of B-cell dysregulation that is observed in infected individuals. HIV virions complexed with complement and antibody can bind B cells through the complement receptor CD21, and HIV virions and proteins, including gp120 and Nef, can also interact directly or indirectly with B cells.
Indirect effects of HIV viraemia on B cells include B-cell hyperactivity (as manifested by hypergammaglobulinaemia), increased B-cell polyclonal activation, increased B-cell turnover, increased expression of activation markers and of markers that are associated with activation-induced apoptosis, increased frequency of B-cell malignancies and increased differentiation of B cells to plasmablasts.
HIV viraemia with CD4+ T-cell lymphopenia is associated with an increased frequency of immature transitional B cells. This increase is also associated with increased serum levels of interleukin-7.
HIV viraemia leads to B-cell exhaustion, as manifested by increased expression of multiple inhibitory receptors, altered expression of homing receptors, decreased cell division and somatic hypermutation in vivo, decreased proliferative and effector properties in vitro and enrichment of HIV-specific responses in the exhausted B-cell compartment.
Although most B-cell perturbations in HIV-infected individuals are attributed to viraemia and are reversible by ART, one important exception is the loss of memory B cells. All stages of HIV infection are associated with a decrease both in the frequency of resting memory B cells and of B-cell responses against T-cell-dependent and T-cell-independent antigens.
Many B-cell perturbations observed in HIV infection also arise in various infectious and non-infectious disease settings that involve immune dysfunction. Several human diseases that affect B cells show dysregulation of immature transitional B cells, whereas others show dysregulation of memory B cells, with alterations that are similar to B-cell exhaustion and activation-induced terminal differentiation.

Author affiliations
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, Maryland 20892, USA.
Correspondence to: Susan Moir1 Email: smoir
Title: Re: Could this be the holy grail ?
Post by: veritas on March 28, 2009, 05:00:30 am

Hiv vaccine research update -------  worth the long read:


http://www.hivvaccineenterprise.org/_dwn/news/2009.01.21_Enterprise_Science_Committee_Minutes.pdf
Title: Re: Could this be the holy grail ?
Post by: Matts on March 30, 2009, 03:00:32 am
Thank You for Your postings about Anti-PS, this topic is very interesting


Let's wait for some results about the Bavi(3g4,2g12,PGN 635,1N11,former Tarvacin) HIV/HCV trial.
Possibly this mAb is not so good against HIV as against cancer or HCV, but there will be better mAbs
in the future.

The Peregrine trials so far are all small, not randomized, uncontrolled and not further than phase II.
Nevertheless Bavituximab has potential against all enveloped viruses (HepC, HIV, Influenza/Avian Flu, CMV, RSV, Lassa Fever), solid tumor types and unenveloped viruses.
Peregrine and DTRA have a biodefence contract of 44Mio$ against viral Hemorrhagic Fevers (Ebola, Marburg, Lassa). Maybe Anti-PS will be the '"Magic bullet" the people are looking for 100 years'. Time will tell.


The Duke/CHAVI/Barton Haynes/Gates/Peregrine/NIH collaboration and their new "SuperBavi" PGN632 [11.31] have even much better results against HIV than all other anti-PS. New Results are expected
within the 1st half of 2009.

-http://www.investorvillage.com/smbd.asp?mb=1773&mn=705&pt=msg&mid=6497373 (http://www.investorvillage.com/smbd.asp?mb=1773&mn=705&pt=msg&mid=6497373)



At the Cowen Conference in Boston (march) they told bavituximab could be used in near future as ' post-exposure- treatment and topical microbizide'. At the moment only Barton Haynes (Duke) knows the possible potential of Mab against HIV. Duke and CHAVI decide what and when they publish something. Peregrine provides the best Mabs, but the HIV/HCP trial and the research is done by Duke. I hope we will hear more soon and Mabs can bring a vaccine and prophylactic treatment in the future.

http://investorshub.advfn.com/boards/read_msg.aspx?message_id=36488065 (http://investorshub.advfn.com/boards/read_msg.aspx?message_id=36488065)




- A blog about Anti_ps:

http://anti-ps.blogspot.com/search?q=hiv (http://anti-ps.blogspot.com/search?q=hiv)


- News about Peregrine and their mAbs:

http://investorshub.advfn.com/boards/board.aspx?board_id=2076 (http://investorshub.advfn.com/boards/board.aspx?board_id=2076)
 







Title: Re: Could this be the holy grail ?
Post by: georgep77 on March 30, 2009, 07:44:11 pm

-http://www.investorvillage.com/smbd.asp?mb=1773&mn=707&pt=msg&mid=6535688 (http://www.investorvillage.com/smbd.asp?mb=1773&mn=707&pt=msg&mid=6535688)

 
Can somebody explain me the graphs from: Bavi vs. Duke-PPHM mab 11.31

                                 Thanks      ;D
Title: Re: Could this be the holy grail ?
Post by: Matts on March 30, 2009, 09:20:00 pm
sorry this was a wrong link

http://www.investorvillage.com/smbd.asp?mb=1773&mn=705&pt=msg&mid=6497373 (http://www.investorvillage.com/smbd.asp?mb=1773&mn=705&pt=msg&mid=6497373)


Tri-mab are the monoclonal antibodies 2G12(Bavi),2F5 and b12. CL1, P1, IS4 are also mAbs. The newest is Duke's PGN632 a.k.a. 11.31, 1000 times stronger than all other mAbs. But so far not tested in humans.


From Dr Moody’s Abstract, AIDS'08/Capetown 10-14-08 :
“…In contrast, B2GPI-indep. anti-lipid mAbs (PGN632, P1, IS4, CL1) inhibited HIV-1 primary isolate infection of PBMC. The most potent mAb PGN632 inhibited 7/7 B & C clade HIV-1 isolates (IC80s<0.02-0.16 mg/mL) and SHIV-SP162P3. Cell preincubation and virus capture studies showed the mAbs acted at host cell surfaces to inhibit HIV-1 infection. Immunofluorescence of CD4þ T cells showed the mAbs bound to lipid rafts…”

NEUTRALIZING ANTIBODIES TO THWART HIV (NIAID 1-6-09)…
“…they [IS4, CL1, P1, PGN632=’most-potent, aka ‘11.31’] neutralized virus in the PBMC assay, apparently through release of b-chemokines (MIP1a, MIP1b) by monocytes in the culture. Such chemokines interfere with virus entry through the CCR5 receptor. Furthermore, neutralization could be reverted by antibodies against MIP1a & MIP1b. These anti-lipid antibodies stick to the host target cell and not the virus to prevent infection…”
http://www3.niaid.nih.gov/topics/HIVAIDS/Research/vaccines/reports/aidsvac2008.htm

= = = = = = What’s PBMC ?:
DUKE Jan’08: “Peripheral Blood Mononuclear Cells (PBMC’s) such as CD4+ cells are invaluable for HIV research. The levels of CD4+ cells, a primary target of HIV infection, can indicate how the immune system is responding to infection over a specific period of time. Use of PBMC’s for HIV research has dramatically increased in recent years as vaccine discovery efforts and multi-center clinical trial networks have expanded.”

CONCLUSIONS
“The AIDS Vaccine 2008 Conf. was primarily focused on basic research. Much of this was dealing with broadly-neutralizing anti-HIV antibodies. The few, rare, known familiar suspects: 2F5, 2G12, b12, were the subject of hundreds of experiments presented at the conference. It seemed that "the way forward" was thought to be via insights into these promising antibodies, 2 of which bind a lipid and the virus, and one of which (b12) binds a sugar that coats a viral protein. According to other interesting data presented at the conference, the antibody b12 is apparently the most potent of the three. Along comes Duke University's researcher [Dr. Tony Moody], and presents data from CHAVI 005 experiments, showing that they've got an antibody [PPHM-Duke Collab. mab ‘PGN632’, aka ’11.31’] which only binds a lipid. This particularly potent antibody is orders of magnitude more potent than even b12, and in subtype-C HIV viruses, ( a very common subtype), the anti-lipid antibody was over 1000 times more potent than b12, 2F5, and 2G12. If that is not enough of a surprise to the field, to continue the out-of-the-box theme, it turns out that this unprecedented incredibly powerful antibody works by sticking to a lipid on uninfected T cells, causes an increase in the beta chemokines that block the CCR5 receptor, which prevent HIV from entering a cell in the first place.”
See: http://anti-ps.blogspot.com
. . .Specifically, http://anti-ps.blogspot.com/2009/01/cape-town-wrap-up-anti-lipid-antibodies.html
------------------------------------------------------
Some general quotes about PS/ Mabs:

 Barton Haynes' previous big shocker in 2005 that got all the money thrown his way (CHAVI & Gates), which made him the #`1 top govt. funded doc in the country, was in Science. That's where he showed that the few rare broadly neutralizing abs found in people bound to not only viral bits, but also phospholipids. He reasoned that those rare BNAbs were not typically made in most people for reasons I've already discussed...
It's taken two short years to move from (most folks) seeing the lipid-binding characteristics of those now-famous rare mabs as a hindrance, to seing them as the KEY....


Or- to re-phrase that - Haynes' original paper sent a shock-wave through the research community, with his data that the extremely rare BNAbs (Broadly Neutralizing Abs) were polyspecific for viral epitopes AND PHOSPHOLIPIDS. The phospholipid binding was seen negatively, surely, as a likely reason for the abs rarity in people, and also with potential safety problems.

I expect the upcoming paper to change the view of that 180 degrees.

In the upcoming paper:

* I expect them to say/prove that targteting phospholipids alone with antibodies can neutralize HIV.
(That's a shocker with implications for many viruses and other diseases).

* I expect them to say/prove that you don't need to target the virus itself.

* I expect them to say/prove that by targeting phospholipids alone with abs you can prevent fusion of the virus with a cell.

* I expect them to say/prove that targeting certain (host-cell) phospholipids on the virus and on virally infected cells with abs is safe.
(Anyone who understands the long-standing foundations of the immunological paradigm will realize how big a change this is).

* I expect them to discuss various details as to the binding specificities of anti-phospholipid abs which further delineate pathogenic and non-pathogenic abs. (That's still quite a grey area among most scientists. Carl Alving, who heads the vaccine dept at Walter Reed has written on this topic in the past couple years and, along with Haynes' team, Pojen Chen and Schroit/Thorpe & PPHM, is on the forefront of the present understanding of what delineates pathogenic and non-pathogenic autoantibodies, and is a proponent of the concept of SAFE abs to phosppholipids). This grey area (at best, presently), is the reason many scientists and others look funny when you tell them about Bavituximab's target.)

* I expect this paper to sound the bell, most authoratively, which ushers in the concept of phospholipid-targeting as a new promising field of therapy, with implications for treating numerous diseases - viral, cancer, and others. I expect it to change how science views disease and disease therapy in a fundamental way, (a little more on that later).

* I expect them to discuss and lend authority to the fact that PS is immunosuppressive, and that covering PS blocks the immunosuppressive signals INITIATED by exposed PS.

* I expect to see specific cytokine data from experiments which detail this PS-initiated immunosuppressive change.

* I expect them to discuss the overwhelming apoptosis in early HIV infection, and that shed vesicles which contain cell membrane phospholipids, expose PS, and that this debris with exposed PS is responsible for blunting the immune system's  response.

* Further, and importantly, I hope they put forth the idea that this way that HIV hides from the immune system, (via exposed PS), is quite possibly a general escape mechanism of disease. I hope to read discussion that, since PS is an early external apoptotic sign, and the cells of the immune system have evolved to recognize it as a fundamental signal for a friendly/homeostasis/pro-growth/repair resonse, that "successful" cancers, viruses, and protozoan parasites seem to have independently evolved to take advantage of this signaling, obviously, because it provides the best advantage allowing them to survive and thrive.

* I expect them to show with compelling data that anti-PS mabs safely deal with this oh so fundamental loop-hole/compromise that has been with us since the dawn of metazoans, (which has been proven to be, as you'd expect, also the dawn of the apoptotic process).

* and I think it'll make the "news" :)

-------------------
we demonstrated the presence of CD3+, CD45+, and
phosphatidylserine (PS)-expressing microparticles in these plasma samples
at the time of viral load ramp-up.

Conclusion: These results demonstrate that at the time of viral load ramp-up
in acute HIV-1 infection, there are elevations in plasma levels of TRAIL, FAS
Ligand, and TNFR2 that were associated with the presence of microparticles
from apoptotic T cells. The presence of these apoptotic markers suggests
apoptosis occurring at the time of initial HIV-1 viral load ramp-up. That PS+
apoptotic cells and microparticles have been reported to suppress antigenspecific
immune responses suggests the hypothesis that immune cell
apoptosis in the very earliest stages of acute HIV-1 infection may delay the
onset of potentially protective anti-HIV-1 immune responses. (CHAVI)

He's (B.Haynes) now recently on record as saying that PS looks to be responsible for a failure of the immune system  to eradicate the HIV virus, or even keep it more in check,
Bavituximab binds the PS exposing microparticles,
(as he showed in the previous CHAVI Admin meeting)....

“We have also been collaborating with researchers at Duke and other institutions to better understand the potential of Bavituximab in an HIV setting. Significant findings of these studies include data supporting Bavituximab binding to mult. strains of HIV and binding to HIV-infected cells


Bavi's MOA - I make that point to further illustrate that recently the general thrust of the overall research into HIV therapy and vaccines, is moving much more in line with Bavi's MOA. It's fascinating, and amazing.


Realize that Haynes is the Director, the top leader, of NIH's whole $300 million CHAVI program, which, along with the Gates $287 million CAVD, both fall under what's called the Global HIV Vaccine Enterprise.

Realize that the reason the money got thrown at Haynes, (crudely put but accurate enough), was due to his MAJOR discovery of the broadly-neutralizing HIV abs found in people naturally stuck to host-cell phospholipids...

and understand that Haynes is the one talking about abundant PS downregulating the immune system's  fight against HIV

and understand that Haynes and others in CHAVI / Gates are working with and generating data on Bavituximab and other PPHM (Peregrine pharmaceuticals)mabs that fall under PPHM's anti-phospholipid platform in his experiments.

Let there be no confusion about that.
------------

in CHAVI 005, they're looking for broadly neutralizing HIV antibodies which target host-cell phospholipids in lupus patients.
in CHAVI 006, they're looking for broadly neutralizing HIV antibodies which target host-cell phospholipids in syphilis patients.
All this is as a model to see if it's worth it to try to design a vaccine that elicits this type of ab in people.
as for "Bavi's MOA" -in CHAVI 012 they're looking into how PS-exposing microparticles may blunt a successful immune response early in HIV infection.
The point of CHAVI & Gates CAVD work is to eventually create a successful VACCINE.
A vaccine is a preventative for something BEFORE your body encounters it.

Bavi and other PPHM mabs are being used to see if it's "worth it" to try to design an immunogen that creates 'natural bavi' in one's body, to stay on the lookout for HIV's potential arrival.
The CHAVI / Gates research may or may not be successful in CREATING A VACCINE. If they are successful, it will take serious time, and serious money.

Any VACCINE work that CHAVI / Gates does with  mabs in their quest to see if they protect from HIV infection, (or alter the immune response in a beneficial way), is IMMEDIATELY applicable  as a THERAPEUTIC.
As I've been saying -
Bavi acts as a therapeutic vaccine for what you've got in ya.

All that data that CHAVI / Gates researchers have been accumulating, has been guiding, and will continue to guide, PPHM's anti-phosphatidylserine antiviral therapeutic (and therapeutic vaccine) research.

Now, it is beyond the scope of the topic of this post, but it is also looking like if and when any HIV vaccine is arrived at, Bavi will again play a role as an ADJUVANT. Due to Bavi's MOA, it should make any vaccine more effective. It should facilitate any immunogen to be 'recognized' more easily.

I hope you realize that Bavi lasts about three days in a person. If you don't have HIV when you get a shot of Bavi, it won't do anything for you down the road. Part of the vaccine research will likely be using combinations of bavi WITH HIV immunogens, much like Thorpes fabulously successful work that so beautifully isolated and illustrated Bavi's immune-modulating vaccination effect against malignant glioma.
This is all well-documented science, illustrated by numerous specific Bavituximab papers and presentations.

I think things will be getting interesting soon,
keep watching! :)













Title: Re: Could this be the holy grail ?
Post by: veritas on March 31, 2009, 08:29:44 am

Matts,

Thanks for your research.

 Anti-ps looks extremely promising and I'm anxiously waiting for interim results on the co-infection trial for Hepc/hiv using 3g4. I realise 3g4 is not the strongest anti-ps mab, however, it should give some indication as to viability with respect to hiv in vivo.

Anti-ps mabs have been dosed in approximately 200 people thus far. The safety data thus far has been incredible----- TOPLINE SAFETY------- in all those dosed. I believe that is due to the targeted aspect of the therapy---- sort of like a smart bomb.

I know CHAVI is going for the homerun---a vaccine. But I believe that will be pretty difficult,due to the incedible viral ramp-up in the first 7to10 days of infection. I do believe that a therapeutic using anti-ps is viable, especially if the immune response can be strong enough to get to the resting infected cd4s.

Lets hope something breaks soon.

v
Title: Re: Could this be the holy grail ?
Post by: veritas on March 31, 2009, 09:43:45 am


Anti-PE, another weapon in the arsenal to fight hiv:

http://finance.yahoo.com/news/Peregrine-Pharmaceuticals-prnews-14794329.html


 v
Title: Re: Could this be the holy grail ?
Post by: Inchlingblue on March 31, 2009, 03:56:55 pm
Veritas (or anyone else who might know):

Is there any way to find out (or estimate) when clinical trials might begin for the use of bavi with respect to HIV? Right now they are in preclinical studies, right?
Title: Re: Could this be the holy grail ?
Post by: veritas on March 31, 2009, 05:12:24 pm

Inch,

It is in clinical trials right now for co-infection with hepc/hiv. However, I believe you were referring to HIV  directly. I believe those trials will come out of the CHAVI group since they have mabs that are more powerful than the 3g4 antibody in the co-infection trials. As to when those trials will start----- they only have funding from the Gates Foundation for another 3 years so they will have to show progress, which I assume will include clinical trials. My guess is that clinical trials ,hopefully, will begin by next year.

v
Title: Re: Could this be the holy grail ?
Post by: Inchlingblue on March 31, 2009, 06:50:51 pm
Thanks V, that's good to know. I was getting my info. from your latest link, above, which states:

"PE belongs to the aminophospholipid family that also includes phosphatidylserine (PS), the target for Peregrine's monoclonal antibody bavituximab that is in a clinical trial for hepatitis C virus (HCV) infection and in preclinical studies for HIV and other viral infections."

I guess apart from being in clinical trial for HCV (as stated above) it's also in clinical trials for HCV/HIV co-infection? From the sound of the above quote it seems Peregrine is planning clinical trials of Bavi and HIV?
Title: Re: Could this be the holy grail ?
Post by: Matts on March 31, 2009, 10:35:57 pm
 Thank You Veritas for the info about the new Anti-PE


The New PPHM PE-Targeting Agent (this one is totally human like PNG635 ,BAVI is chimeric):

...The spectrum of viral treatment for the present invention extends to any virus, whether enveloped or not, DNA or RNA. ....of the invention at least in part block viral replication inside the cell, and/or prevent escape of virus from cells, the invention is not limited to the treatment of enveloped viruses alone, nor to any particular virus, which is an important advantage....
The invention is suitable for treating all viruses that infect vertebrates, particularly humans, and particularly viruses that are pathogenic in animals and humans. The viral infections and associated and resultant diseases that can be treated by the invention include those viruses and diseases set forth in Table J, as exemplified by treating CMV, RSV, arenavirus and HIV infections, and the diseases hepatitis, influenza, pneumonia, Lassa fever and AIDS.

( P.S. Hard to believe)


*http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearch-bool.html&r=1&f=G&l=50&co1=AND&d=PTXT&s1=7,511,124.PN.&OS=PN/7,511,124&RS=PN/7,511,124 (http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&p=1&u=%2Fnetahtml%2FPTO%2Fsearch-bool.html&r=1&f=G&l=50&co1=AND&d=PTXT&s1=7,511,124.PN.&OS=PN/7,511,124&RS=PN/7,511,124)
Title: Re: Could this be the holy grail ?
Post by: Matts on March 31, 2009, 10:47:41 pm


HIV - Phosphatidylserine  - Haynes - Multicomponent vaccine - therapeutic Mab for treatment

 August 20, 2008
The announcement by NIAID Director Dr. Anthony Fauci to scrap the upcoming “PAVE-100″ HIV vaccine clinical trial, (following on the heels of the failed Merck “STEP” HIV vaccine trial), showed yet again how difficult and elusive the goal of an effective HIV vaccine remains.

In the midst of these sobering developments, an important new insight was gained into why experimental HIV vaccines have failed to elicit an adequate immune response. The discovery, published in the August issue of the Journal of Virology (1), came from the leader of NIAID’s “CHAVI” organization, Dr. Barton Haynes of Duke University, who is also a principle investigator of the Gates Foundation HIV vaccine effort.

In their paper, Haynes and colleagues discuss experiments showing that HIV weakens the immune system much faster than previously thought. The primary mechanism responsible for this immunosuppression is an overwhelming amount of what Haynes terms “microparticles”, which are tiny particles shed from the outer membranes of infected and dying cells. This cellular debris accumulates during early HIV infection, and circulates throughout the body blunting the functions of the immune cells that would ideally fight the virus. Popular news articles have discussed this aspect of the Duke researchers’ findings, but the details and broader implications of the team’s discovery have yet to be elucidated in the media.

The paper explains that the microparticles contain the molecule phosphatidylserine (PS) exposed on their surface. PS is a lipid that normally lines the interior of the cell membranes of every cell in our body. As a cell dies, it loses the ability to maintain PS on the inside of the cell membrane. The PS flips to the exterior, where it is perceived by immune cells as a sign of a dying native cell. The Haynes team cite recent data showing how exposed PS appears to be the fundamental signal that shifts the behavior of immune cells into not mounting an antigen-specific attack, since PS is interpreted as a sign of “self” rather than a foreign invader (2). Other researchers have also recently illustrated the suppressive effects of PS on macrophages, the resulting cytokine environment, dendritic cells, and T cells (3-7). It is thus no surprise that recent research has also revealed exposed PS as a feature common to many diverse pathogens (8-22), as if they independently evolved to exploit a similar mechanism of evasion, since it provides the crucial advantage of triggering an inappropriate immune response, facilitating the pathogen’s survival and proliferation.

A review of Haynes’ recent patent applications provides further details that have yet to be published in the journals. In one application, titled “Multicomponent Vaccine” (23), Haynes explains that any future successful HIV vaccine must interrupt this PS-mediated immunosuppressive signaling. A specific goal mentioned is for a vaccine to induce antibodies to PS (anti-PS), thereby blocking the overwhelming immune suppression seen in the Duke research, allowing the viral immunogen in the vaccine the chance to evoke T and B cells which effectively fight the virus.

In yet another recent patent application, Haynes proposes using anti-PS as a promising treatment for people already infected with the virus (24). He discusses the ability of anti-PS monoclonal antibodies to bind to HIV and HIV-infected cells, saying anti-PS “can be safely used as a therapeutic Mab for treatment of HIV infected subjects”, and that it can “broadly neutralize HIV in an unprecedented manner”.

Perhaps the most fascinating comment found in one of Haynes’ many recent patent applications is his suggestion that HIV’s method of immune evasion may be a general escape mechanism utilized by other pathogens (24), and that similar means of therapy may be effective against other diseases. Indeed, a review of the recent major journals corroborates this concept.*


In April, the journal Science published experiments showing that the pox family of viruses, (vaccinia), utilize exposed PS to gain entry into cells (25).

In the March issue of the journal Clinical Cancer Research, scientists from Harvard University discuss experiments in which blocking PS signaling helped facilitate complete melanoma tumor regressions (26).

The protozoan parasites responsible for many of the deadly diseases affecting much of the developing world have been found to rely on exposed PS to successfully avoid the immune system of their host (16-22).

Several cancer researchers have recently published data which bears a striking resemblance to the new findings of the Haynes HIV group, showing a very similar method of systemic immune suppression caused by PS-exposing microparticles shed from tumor cells (29-34), (see also 27, 28).

In another recent Haynes patent application he also discusses PS-exposing microparticles as playing a role in the pathogenesis of several auto-immune diseases as well as atherosclerosis (35), (see also 36-40).

Taken together, these discoveries suggest a new immunological perspective of pathogenesis in general. A paradigm appears to be emerging in which the necessary and admirable flexibility of the immune system has been exploited precisely where it is most vulnerable – when it must commit to a ‘friendly’ response. The recent HIV research by Haynes and colleagues, focusing on PS-induced immune suppression, and the safe therapeutic targeting of exposed PS with antibodies, carries implications of unprecedented broad therapeutic potential.

*http://www.iayork.com/MysteryRays/2008/08/18/quality-and-quantity-once-again-with-vaccination/ (http://www.iayork.com/MysteryRays/2008/08/18/quality-and-quantity-once-again-with-vaccination/)



Sources:http://www.iayork.com/MysteryRays/2008/08/18/quality-and-quantity-once-again-with-vaccination/#comments (http://www.iayork.com/MysteryRays/2008/08/18/quality-and-quantity-once-again-with-vaccination/#comments)
Title: Re: Could this be the holy grail ?
Post by: Inchlingblue on March 31, 2009, 11:48:44 pm
Matts: Thanks for the above. Just curious: what's the date of the article you cut and pasted?
Thanks ;)
Title: Re: Could this be the holy grail ?
Post by: veritas on April 01, 2009, 06:00:54 am

 Matts,

  I thought you would like that anti-pe patent.

  I trust you read the world patents submitted by Duke at the beginning of this thread ------- one for the multi-component vaccine and the other for a therapeutic using is4.  Since most of the pre-clinical work is being done by CHAVI for HIV, I'm sure they will be involved in the clinical trials when they come up with their final "mix".

  Inch,

  It wouldn't surprise me if CHAVI is trying to incorporate anti-pe in their quest for the cure. Thorpe's lab is part of the CHAVI group.

  v

Title: Re: Could this be the holy grail ?
Post by: Matts on April 01, 2009, 11:50:52 pm
These 2 patents look really good, especially the multicomponent vaccine.

targeted at overcoming: i) HIV diversity, ii) tolerance constraints of neutralizing antibody induction, and iii) apoptotic  induced immunosuppression (FAS, TRAIL,TNF).

Maybe CHAVI can be successfull in some years.
Title: Re: Could this be the holy grail ?
Post by: veritas on April 08, 2009, 05:08:27 am

Fauci believes vaccine possible:


http://www.msnbc.msn.com/id/29898087/

Rapid viral buildup in early infection biggest obstacle to preventative vaccine.
Title: Re: Could this be the holy grail ?
Post by: veritas on April 11, 2009, 05:20:25 am



CCR5 LIGAND CCL3 (MIP-1-ALPHA)
UP-REGULATES APOBEC3G



"It has been established that the HIV-1-inhibitory activity of A3G is neutralized by Vif (9, 10, 11, 12). This interaction has raised therapeutic potentials, by either inhibiting Vif activity or boosting A3G levels above the neutralizing capacity of Vif to inhibit virus replication (5, 26)."



"Stimulation of primary human CD4+ T cells or immature DC with CCL3 [aka: mip-1-alpha] showed a dose-dependent increase in A3G mRNA expression"



"These findings suggest that CCL3 may not only block and down-regulate CCR5, thereby inhibiting pre-entry of HIV-1 (27, 28), but also stimulate A3G expression, which inhibits postentry replication of HIV-1."



"Thus, stimulation of the CCR5 molecule, which is the major coreceptor of R5 strains of HIV-1 (38, 39), or the CD40 (25) molecule, which is part of a major costimulatory pathway, up-regulates A3G and results in postentry inhibition of HIV-1 replication. This novel finding may be important in enhancing the innate intracellular anti-HIV-1 response and provides a complementary strategy in protective and therapeutic immunization against HIV-1."


http://www.jimmunol.org/cgi/content/full/178/3/1671
Title: Re: Could this be the holy grail ?
Post by: Matts on April 11, 2009, 08:50:03 am
Maybe zinc could help to inhibit vif :) Link (http://www.freepatentsonline.com/y2008/0206357.html?query=PN/20080206357%2520OR%252020080206357&stemming=on)

Thomas Lehner has developed a trimolecular construct for microbizides and vaccines: http://ec.europa.eu/research/health/poverty-diseases/projects/134_en.htm (http://ec.europa.eu/research/health/poverty-diseases/projects/134_en.htm)

T.Lehner and B.Haynes as part CAVD: p.13  Link (https://chavi.org/wysiwyg/downloads/Haynes_Admin_meeting_January_25,_2007.pdf)
Title: Re: Could this be the holy grail ?
Post by: veritas on April 12, 2009, 05:21:34 am

Matts,

Kings college is part of the CHAVI group --- nice find !


https://chavi.org/modules/chavi_sites/index.php?id=18

From your link:

Coordinator:
Thomas Lehner, MD, FRCPath, F Med Sci
Professor of Basic & Applied Immunology, Mucosal Immunology Unit, Guy’s,
King’s & St. Thomas’ Medical & Dental School, Guy’s Hospital, Guy’s Tower
Floor 28
London SE1 9RT
United Kingdom
Phone: 44 207 188 3072
Fax: 44 207 188 4375
Email : thomas.lehner@kcl.ac.uk
Website: www.kcl.ac.uk
 
Title: Re: Could this be the holy grail ?
Post by: veritas on April 13, 2009, 12:46:38 pm
CAVD Feb 1, 2009

 Annual and Interim Progress Report Summaries
Principal Investigator: Thomas Lehner
Project: Allogeneic – HIV Mucosal Vaccine Strategy Against HIV, Utilizing Innate and Adaptive Immunity
 
Submitted February 1, 2009 (Interim Report)
The aim of the project is to establish if xeno-immunization and allo-immunization of macaques can prevent or contain infection after challenge with SHIVSF162.  In the xeno-immunization experiment the vaccine consisting of HLA-class I and HLA-class II and/or HIVgp140, SIVp27 and HSP70 formulated with dextran into Dextramers was prepared, mixed with a co-adjuvant (Titermax Gold) and administered subcutaneously (x4) to 4 groups (one without Titermax) and 1 control group, each consisting of 8 macaques, over a period of 16 weeks.  The macaques were challenged IV with SHIVSF162P4, 4 weeks after the last immunization and the viral load was monitored.  The results showed significant decrease in viral load or total prevention of infection against the heterologous SHIVSF162P4 in one group of macaques compared with the unimmunized control group over the post-challenge period of 10 weeks (p<0.001 to p<0.05).  Importantly, the protected group of macaques was the one immunized with both HLA-class I + II and HIVgp140 + SIVp27 linked to HSP70 given in the Titermax adjuvant.  Sterilizing protection was not achieved in the other 3 immunized groups, suggesting that excluding any HLA or SHIV antigens fails in eliciting significant protection.

These promising results were then evaluated by examining a number of immune functions.  High titres of complement-dependent neutralizing antibodies were elicited in 3 of the immunized groups with the co-adjuvant compared to pre-immunization (p<0.0001).  Indeed, significant inverse correlation was found between the cumulative viral load (over the 10 weeks of post-viral challenge) and neutralizing antibodies (p<0.05).  High levels of antibodies were induced to the immunizing HLA-class I (A1, A2, A3 and A11) and HLA-class II (DR4) antigens (p<0.01), demonstrating that the recombinant HLA antigens are potent immunogens. As with the neutralizing antibodies, a significant inverse correlation was found between cumulative viral load and the HLA-I antibodies and this appeared to be specific to the protected group of macaques (p<0.001-p<0.05).  Surprisingly, CCR5 antibodies were also elicited in the protected group of macaques and this was associated with a significantly decrease in CCR5 expression in CD4+ T cells (p<0.01), consistent with a decreased infectivity of the primary cell target.  Among the innate anti-viral factors APOBEC3G was investigated and found to be significantly increased in the immunized groups, again with an inverse correlation with the cumulative viral load (p<0.0001). Thus, both antibodies and innate cellular factors were identified in immunized macaques and further cellular parameters are being analysed.

Allogeneic immunization with recombinant macaque MHC class-I and class-II antigens and the other components has also been completed and the immune responses are in the process of being evaluated.  The animals have been challenged and the viral load is being monitored. 

 
 

 
 
Title: Re: Could this be the holy grail ?
Post by: Tower311 on April 15, 2009, 03:44:30 pm
I just read the whole thing.  Man, did that make my heart smile.  It's so exciting to think that something like this COULD happen.  I know it's not done.  But, man, can you imagine if humans figured out how to defeat viruses?  Not just this one, but all of 'em?  That's major.  MAJOR.

It's really far out there, but why not?  It's possible.  We're smart.  We can do it.  I just feel great right now.  Just great.
Title: Re: Could this be the holy grail ?
Post by: veritas on April 16, 2009, 05:45:30 am

 Tower311,

  The research is compelling and amazing. As if retro-virus weren't enough, the therapy seems to work well against cancer. Bavituximab is entering phase ll cancer trials against many cancer indications (including lung cancer).

   I'm glad you took the time to read the entire thread. I believe one can see how cautiously the research is being unfolded and how so many of the top researchers in both immunology and oncology are researching anti-ps.

   I also have not been able to find a dissenting paper concerning the therapy. If anyone can find one please post.

   Let's hope development picks up speed so anti-ps can start saving lives and relieving the suffering of many people. We need a Holy Grail!

   v

Title: Re: Could this be the holy grail ?
Post by: veritas on April 19, 2009, 04:08:47 pm

anti-ps (Bavituximab) is a targeted cancer therapy:

http://therpmreport.com/Free/f27af8ed-2215-474b-9700-fcc71e01193d.aspx?utm_source=RPMel

Let's hope they fast track Bavi -------

v
Title: Re: Could this be the holy grail ?
Post by: veritas on April 20, 2009, 08:23:14 am

11 of 17 evaluable  patients respond to Bavituximab in phase ll lung cancer trial out of 25 say preliminary results.  Dosing to go on:

http://finance.yahoo.com/news/Peregrine-Pharmaceuticals-prnews-14969179.html?.v=1

Anti-ps (Bavituximab) uses the same moa for viral disease. Anxiously awaiting preliminary data from co=infection trial for HIV/HEPC.

FAST TRACK ANTI-PS NOW !

v

Title: Re: Could this be the holy grail ?
Post by: veritas on April 21, 2009, 08:23:52 am

 "Dendritic cells are the professional antigen-presenting cells of the immune system and they play a crucial role in initiating adaptive immune responses. Dendritic cells must be mature, or activated, to be effective, yet tumors and other pathogens such as viruses often possess the ability to undermine this maturation, thereby suppressing the immune response. The results presented today suggest that by blocking exposed PS, anti-PS antibodies have the potential to promote dendritic cell maturation in the body and thereby stimulate a more effective immune response."

http://finance.yahoo.com/news/Studies-Presented-at-AACR-prnews-14981130.html?.v=1

ANTI-PS SHOULD BE FAST TRACKED NOW!

How does the above relate to HIV?

http://jvi.asm.org/cgi/content/abstract/83/8/3486

"Dendritic cells (DCs) are the first in vivo targets of MMTV infection. In this study, we demonstrate that mA3 expressed in target cells restricts MMTV infection in DCs ex vivo and in vivo. By comparing infection of DCs from mA3+/+ and mA3–/– mice with one-hit viruses, we show that mA3 expression in target cells blocked MMTV infection at a postentry step and acted together with virion-packaged mA3 to inhibit infection."

ANTI-PS IS WORKING AND SHOULD BE FAST TRACKED NOW!

v
Title: Re: Could this be the holy grail ?
Post by: veritas on April 21, 2009, 01:59:42 pm

DCs and hiv ---- another study:

http://jem.rupress.org/cgi/content/full/203/13/2887

Ralph Steinman, Rockefella University, is part of the CHAVI Group.


JBM Blog

v

Title: Re: Could this be the holy grail ?
Post by: Matts on April 21, 2009, 03:32:56 pm
I'm glad that You mention R. Steinman. The  DEC205-VAC Project is very promising and will possibly go into human trials still in this year.

A lot of information from Rockefeller University: Link (http://www.rockefeller.edu/labheads/steinman/research.php)

Prof. Klaus Überla DEC-VAC "Why are we still waiting
for the HIV vaccine?" :Link PDF (http://www.ruhr-uni-bochum.de/rubin/europe/pdf/beitrag3.pdf)

Ralph M. Steinman: "Dendritic cells and vaccines" :Link (http://ukpmc.ac.uk/articlerender.cgi?artid=1235230#top)


"DEC-205 receptor on dendritic cells mediates presentation of HIV gag protein to CD8+ T cells in a spectrum of human MHC I haplotypes" : Link Pubmed (http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1783096#top)


"Dendritic Cells In Vivo: A Key Target
for a New Vaccine Science" by R. Steinman:Link PDF (http://download.cell.com/immunity/pdf/PIIS1074761308003671.pdf?intermediate=true)   Celldex Therapeutics (Steinamn, Nussenzweig): Link (http://www.celldextherapeutics.com/wt/page/infectious_disease)

Sarah Schlesinger, Rockefeller about dendritic vaccine:Link Videopage (http://bigthink.com/drsarahschlesinger/ideas)

"Improved Vaccine Efficacy via Dendritic Cells and Flavivirus Vectors"- Bill&M. Gates Foundation:Link Project Description (http://www.grandchallenges.org/NewVaccines/Challenges/DesignAntigensforProtectiveImmunity/Pages/DendriticCells.aspx#top)
Title: Re: Could this be the holy grail ?
Post by: Inchlingblue on April 21, 2009, 05:23:36 pm
One of the links above from Matts, says "The aim of vaccines must therefore be to
counteract this fatal development at an early stage."

I hope this does not mean that these vaccines targeting dendritic cells are mant only as preventve or very ealry and not as therapeutic vaccines. I wonder how they define "early stage."
Title: Re: Could this be the holy grail ?
Post by: John2038 on April 21, 2009, 05:45:16 pm
Peregrine Pharmaceuticals Reports Positive Preliminary Data From Phase II Bavituximab Lung Cancer Trial (http://www.bio-medicine.org/medicine-technology-1/Peregrine-Pharmaceuticals-Reports-Positive-Preliminary-Data-From-Phase-II-Bavituximab-Lung-Cancer-Trial-4175-1/)

EDIT

Eish, already posted by Veritas.  :D
Title: Re: Could this be the holy grail ?
Post by: veritas on April 22, 2009, 05:07:40 pm
How does anti-lipid mab and dendritic cells interact to inhibit hiv? Please read below:


The Potential of Anti-Lipid Mab Induced Dendritic Cell Maturation


An antibody that targets a plasma membrane lipid has shown to be the most potent and most broadly HIV-neutralizing antibody yet found. Duke University researchers, led by Dr. Bart Haynes, funded by the Gates Foundation and the NIH's CHAVI, in work from the CHAVI 005 protocol which seeks to understand why auto-immune patients are statistically less prone to HIV infection and AIDS, presented data at the AIDS Vaccine 2008 conference in Cape Town, SA (which has yet to be published in a peer reviewed journal, but was chosen as a highlight by the conference rapporteur and is summarized on the Global HIV Vaccine Enterprise website) illustrating the exceptionally powerful HIV-inhibiting properties of this non-pathogenic monoclonal 'auto-antibody', currently named 11.31, aka: PGN632.

As illustrated in the rapporteur session of the Gates-funded AIDS Vaccine 2008 conference, the mab was more broadly-neutralizing, and was much more potent than the well-known rare broadly neutralizing mabs 2F5, 2G12, b12 combined.

Like the well-known rare BNAb's 2F5 and 4E10, 11.31/PGN632 binds host-cell lipids. But while 2F5 and 4E10 bind lipids and a viral epitope, 11.31/PGN632 strictly binds lipid. It turns out that the mab binds to exposed anionic lipids on lipid rafts of uninfected CD4+ T cells. Via mechanisms as yet still vague, (possibly via monocytes as discussed in the NIAID review of the mab), the Duke researchers led by Tony Moody found that this mab causes an increase in the beta chemokines MIP-1-alpha and MIP-1-beta, (aka: CCL3 & CCL4), which bind the CCR5 receptor, blocking HIV from entering its target cells.

The role of beta chemokines with regard to HIV infection have been researched by many scientists in the past decade, including of course Robert Gallo's group, who have published extensive data pointing to the chemokines as potential correlates of immune protection to HIV.

Interestingly, Tom Lehner & team at King's College, London, have recently published data illustrating that the CCR5 ligand MIP-1-alpha (as well as HSP70) cause an increase in intracellular APOBEC3G, with the potential to affect HIV post-entry.

Last fall, NIH researchers also surprisingly found that APOBEC3 affects antibody responses.

In short, according to Duke scientists funded by the Bill and Melinda Gates Foundation, this anti-lipid antibody 11.31 / PGN632 causes an increase in CCR5 ligands which potently inhibits HIV entry, and according to research at King's College, CCR5-tickling in turn up-regulates intracellular APOBEC3, which could potentially mutate existing intracellular virus to death.


Other recent data points to protection of mature dendritic cells from HIV, again via increased APOBEC3. Indeed, none other than Dr. Ralph Steinman, co-discoverer of dendritic cells and now a CHAVI Scientific Advisor as well as Global Vaccine Enterprise Science Committee member, has suggested that somehow facilitating an increase in mature dendritic cells at the mucosal point of HIV entry may protect from infection. This makes recent data on 11.31/PGN632 all the more interesting.

The most recent data on antibody 11.31 aka:PGN632 was presented this week, (April 20th, 2009), at the 100th AACR annual conference in Denver. The antibody has been found to facilitate dendritic cell maturation. The mab was found to increase costimulatory molecules on DC's and also increase inflammatory cytokines and chemokines. To quote the abstract,

"11.31 significantly increased the expression of maturation markers CD40, CD80, CD86 and MHC II on the surface of dendritic cells. 11.31 also significantly increased production of IL-2, IL-6, TNFa, GM-CSF and MIP-1B by immature dendritic cells."

These mechanisms strongly imply the mab's potential as an adjuvant in vaccines against viruses and tumors. Or in the case of HIV, perhaps a combination microbicide / mucosal vaccine, somewhat similar to Lehner's work which includes mucosal vaccination with CCR5 ligands, and Steinman's suggested goal of mature dendritic cells at the mucosal point of viral introduction.

With the data presented at the AIDS Vaccine 2008 conference outlining the antibody's unprecedented potency of HIV inhibition, combined with details presented this week clarifying the mechanisms involved - specifically up-regulating costimulatory molecules on dendritic cells as well as expression of inflammatory cytokines and chemokines, could this phosphatidylserine (PS) targeting antibody 11.31 / PGN632 which binds lipid rafts on uninfected T cells, besides preventing HIV cell entry via beta chemokines as shown by Duke scientists, could it increase efficient antigen presentation by DC's, and stimulate activation of CD8+ T cells? Both of these actions are clearly implied by the mab's DC maturation details listed above.

Finally, could these same mechanisms induce the activation of latent cells harboring the HIV reservoir, waking up the dormant virus and directing it's self-destruction via beta chemokine-induced increased intracellular APOBEC3?

jbm/blog

ANTI-PS SHOULD BE FAST TRACKED!

v



.
Title: Re: Could this be the holy grail ?
Post by: veritas on April 22, 2009, 05:12:17 pm


Anti-ps takes on prostate cancer model and reduces tumors by 90%:

http://finance.yahoo.com/news/Data-Presented-at-AACR-Annual-prnews-14997163.html?.v=1


ANTI-PS SHOULD BE FAST TRACKED!

v
Title: Re: Could this be the holy grail ?
Post by: georgep77 on April 22, 2009, 05:59:33 pm

Anti-ps takes on prostate cancer model and reduces tumors by 90%:

Even in an mouse model, 90% is awesome    :o
Title: Re: Could this be the holy grail ?
Post by: hotguyinTX on April 24, 2009, 01:46:26 am
"Via mechanisms as yet still vague, (possibly via monocytes as discussed in the NIAID review of the mab), the Duke researchers led by Tony Moody found that this mab causes an increase in the beta chemokines MIP-1-alpha and MIP-1-beta, (aka: CCL3 & CCL4), which bind the CCR5 receptor, blocking HIV from entering its target cells.

The role of beta chemokines with regard to HIV infection have been researched by many scientists in the past decade, including of course Robert Gallo's group, who have published extensive data pointing to the chemokines as potential correlates of immune protection to HIV."

This is quite troubling to me because there are studies showing otherwise, showing no evidence that it suppresses HIV or worse, even promote HIV replication. How do they determined that beta chemokines work?

Here are a few studies:

Title: Re: Could this be the holy grail ?
Post by: veritas on April 24, 2009, 05:46:13 am
hotguyinTX,

I believe you will find your answer here, as reported by NIAID:

http://www3.niaid.nih.gov/topics/HIVAIDS/Research/vaccines/reports/aidsvac2008.htm

'Neutralizing antibodies to thwart HIV
Dennis Burton of the Scripps Research Institute discussed how administering neutralizing antibodies can safeguard monkeys against infection with an HIV–SIV chimeric virus (SHIV). IgG1b12, a broadly neutralizing antibody competes for the same niche on the HIV shell glycoprotein, gp120 that serves as the initial contact point for CD4, thereby blocking viral entry into cells bearing CD4 on their surface. High concentration of b12 infused intravenously into monkeys prevents SHIV infection through the vaginal route (Nature 449: 101, 2007). Studies with another broadly neutralizing, 2G12 that binds to a dense cluster of carbohydrates on gp120, revealed that 2G12 protected monkeys at 100 fold lower concentration than b12, thus implying that the epitope targeted by 2G12 may be more beneficial or 2G12 is a more effective antibody. In addition, multiple low dose challenge experiments in monkeys to more closely mimic human HIV infection showed that b12 provided passive protection effectively at much lower concentrations that those employed in previous experiments.


Tony Moody of Duke University School of Medicine established a panel of b2-glycoprotein I independent anti-lipid monoclonal antibodies from auto-immune disease patients. These antibodies failed to neutralize HIV in the standardized TZM-bl reporter cell line assay. However, they neutralized virus in the PBMC assay, apparently through release of b-chemokines (MIP1a, MIP1b) by monocytes in the culture. Such chemokines interfere with virus entry through the CCR5 receptor. Furthermore, neutralization could be reverted by antibodies against MIP1a and MIP1b. These anti-lipid antibodies stick to the host target cell and not the virus to prevent infection. A vaccine that induces such antibodies may not be able to directly neutralize HIV but it may reduce virus spreading."

Could you repost the studies you found, it looks like they didn't take. Thanks.

v
Title: Re: Could this be the holy grail ?
Post by: veritas on April 24, 2009, 09:26:49 am

More info as to why anti-ps will get around that problem of short mabs:

"With the Caltech discovery in mind, it's important to note the fundamental difference of a lipid-targeting approach to virus neutralization. Until quite recently, all attempts by scientists to develop powerful neutralizing antibodies against viruses were aiming at the virus, which of course seems logical. Rather than targeting the traditional common-sense target of the virus spikes poking up through the ocean of host-cell lipid goop, anti-lipid antibodies do not aim for the viral spikes or anything directly to do with viral proteins at all. Anti-lipid antibodies target the goop. There's no need for antibody stretches. That "goop" is made up of lipids from our own cell membranes which get stuck to the virus as it exits one of our cells. It was traditionally considered a waste of time, or possibly worse, to deliberately target lipids with antibodies. That opinion is quickly changing. It turns out that the host-cell lipids exposed on viruses may play a powerful role in inhibiting a successful immune response, as well as an active role in viral entry into cells."


http://1.bp.blogspot.com/_ekJ44PA8pQc/SfG06j17ocI/AAAAAAAAAQw/tNqtG2PvfB4/s1600-h/hiv+virion+cartoon+labeled.JPG

jbm/blog


v






















Title: Re: Could this be the holy grail ?
Post by: hotguyinTX on April 25, 2009, 12:51:19 am
Hi! Not sure why the links were missing.. I probably forgot to copy and paste the links!

While I am extremely excited, remember that antibodies can be extremely toxic and can cause long term damage to our immune systems. Take this for an example:

"TGN1412 (also known as CD28-SuperMAB) is the working name of an immunomodulatory drug which was withdrawn from development, originally intended for the treatment of B cell chronic lymphocytic leukemia (B-CLL) and rheumatoid arthritis.[1] It is a humanised monoclonal antibody that not only binds, but is a strong agonist for the CD28 receptor of the immune system's T cells."

http://en.wikipedia.org/wiki/TGN1412

Result? It made them deathly ill even tho it was administrated at a subclinical dose (500 times lower than the safe dose in animals).

Apparently, there's a lot about our immune system that we have not fully understand. What's so difficult is that we know for a fact that we have people who seem to be resistent to HIV infection despite repeated exposure and we are STILL NOT sure about their resistence.. is that possible that they simply got lucky? Or is there immune system difference involved? I am sure you have heard of delta32... but we have reports of them getting infected with HIV anyway... are we REALLY confident that it was that isolated gene mutation that made them mroe resistent or is that genetic mutation having some interesting effects on immune system which in turn makes them more resistent to hiv infection or if infected, progress much slower?

HIV is a fascinating virus because it has puzzled scientists and it doesn't seem to behave like a typical retrovirus... we get flu and if we get it, we either get sick or die... but a lot of people are immune to infection... and when we DO get sick, we usually get rid of the flu virus and we're just fine afterwards. That's not the case with HIV yet we know for a fact, there are two documented cases where a person who got transplant have been "cured" of HIV - no traces of HIV left. Why? Even more puzzling, if delta32 was supposed to protect you from one strain of HIV, why did it "cure" those HIV+ patients even tho they have at least two different strains and one of them does not need the um... let me think.. CR5 receptors (not recalling right off). And why do some people with delta32 still get infected with HIV?

Remember the vaccine failure when vaccinated people were more likely to get infected? Why? Is priming our immune system actually more dangerous than making our immune less active? And now I am hearing that a systemic autoimmune disease may "protect" patients from getting HIV.

Hopefully we'll get to the point where we will have a coherent theory on HIV and its effect on immune system AND also on how immune system really work. But I sure hope as hell that we have SOMETHING to treat and possibly cure HIV/AIDS!
Title: Re: Could this be the holy grail ?
Post by: veritas on April 25, 2009, 04:44:52 am
I'm familiar with the TGN1412 problem. I believe the mab was tested in the UK. The reaction occured within hrs of the patients being dosed, causing a cytokine storm in the patients bodies. Such a reaction has not occured with Bavituximab. As a matter of fact quite the opposite. All the safety data so far has been top line in all patients  dosed(over 200) some of which were terminal cancer patients.

How about those links?

v

Title: Re: Could this be the holy grail ?
Post by: veritas on April 27, 2009, 08:27:54 am

Anti-ps now attacks breast cancer, see phase ll results:


http://finance.yahoo.com/news/Peregrine-Pharmaceuticals-prnews-15038173.html?.v=1

same moa for viral -------

ANTI-PS SHOULD BE FAST TRACKED NOW!

v
Title: Re: Could this be the holy grail ?
Post by: veritas on April 28, 2009, 08:59:51 am






 
The strongest anti-ps mabs to date:




 
From the Wires
Affitech-Discovered Anti-PS Antibodies in Development by Peregrine Pharmaceuticals Show Excellent Functionality in Preclinical Studies

By: PR Newswire
Apr. 28, 2009 06:00 AM
 
   

 

OSLO, Norway, April 28 /PRNewswire/ -- Affitech AS, the human antibody therapeutics company, announced today that preclinical data on two fully human anti-PS (phosphatidylserine) antibodies were presented by its collaboration partner Peregrine Pharmaceuticals at the 100th Annual Meeting of the American Association for Cancer Research (AACR) 2009 held during April 18 - 22, 2009 in Denver, CO. The preclinical studies of PGN635 and PGN632 provided further confirmatory evidence that the anti-tumor effects observed with anti-PS antibodies reflect their immunomodulatory mechanism of action, including their ability to stimulate the immune system. Additionally, PGN635 demonstrated encouraging signs of efficacy in a preclinical model of prostate cancer. Both antibodies were isolated using Affitech's unique MBAS (Molecule Based Antibody Screening) method for selection and improvement of fully human antibodies from large libraries.

The researchers from Peregrine, Affitech and UT Southwestern Medical Center confirmed previous observations that in vitro, anti-PS antibodies stimulate the tumor microenvironment to recruit monocytes and other immune cells to the tumor with resulting anti-tumor effects, most likely via cell-mediated mechanisms such as antibody-dependent cell-mediated cytotoxicity (ADCC). Their data further defined the role of anti-PS antibodies in mediating tumor cell cytotoxicity and the tumor microenvironment, showing that the anti-PS antibody induced a sequential release of cytokines and beta-chemokines and stimulated enhanced macrophage recruitment to tumors. Furthermore, the researchers showed that in vitro, PGN635 induced antibody-dependent death of endothelial cells, the same cell type found in the tumor vasculature, a key target of anti-PS cancer therapy. The studies also demonstrated the anti-tumor potential of PGN635 in vitro and in a number of animal cancer models. Specifically, in a mouse model of prostate cancer, treatment with a mouse equivalent of PGN635 significantly retarded the growth of tumors by more than 90%.

In a separate study, researchers from UT Southwestern Medical Center (Peregrine's academic collaborators) and Affitech demonstrated in in vitro studies that immature dendritic cells cultured in the presence of PGN632 exhibited a significant increase in the production of inflammatory cytokines and chemokines. PGN632 also induced an increase in the expression of cell-surface molecules that are indicative of mature dendritic cells and that assist in antigen presentation functions, as well as in stimulating T-cell proliferation.

"These results demonstrate the efficiency and robustness of Affitech's range of antibody discovery platforms which include CBAS (Cell Based Antibody Screening) in addition to MBAS. They are being applied with increasing success to build proprietary oncology pipelines for both collaborators such as Peregrine and for ourselves," said Dr Martin Welschof, CEO of Affitech AS.

Commenting on the research progress of the antibodies and Peregrine's collaboration with Affitech, Steven King, President and CEO of Peregrine Pharmaceuticals said, "As leaders in the development of anti-PS antibodies for both oncology and anti-viral applications, we are delighted with these promising data for our fully human anti-PS antibodies from Affitech. They are the result of our well-established and highly productive collaboration and we look forward to continuing success in this and other projects."

For more information on Peregrine's anti-PS programs, visit http://www.peregrineinc.com
 


Title: Re: Could this be the holy grail ?
Post by: veritas on April 30, 2009, 05:19:24 am

Anti-ps takes aim at melanoma:

Tumor-derived microvesicles modulate the establishment of metastatic melanoma in a phosphatidylserine-dependent manner


Luize G. Lima, Roger Chammas, Robson Q. Monteiro, Maria Elisabete C. Moreira, Marcello A. Barcinski


Division of Experimental Medicine, National Cancer Institute, RJ, Brazil
Institute of Medical Biochemistry, Federal University of Rio de Janeiro, RJ, Brazil
Laboratory of Experimental Oncology, School of Medicine, University of São Paulo, SP, Brazil
Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, SP, Brazil


L.G. Lima et al., Tumor-derived microvesicles modulate the establishment of metastatic melanoma in a phosphatidylserine-dependent manner, Cancer Lett. (2009), doi:10.1016/j.canlet.2009.03.041


ABSTRACT:
Exposure of phosphatidylserine (PS) on cellular membranes and membrane-derived microvesicles stimulates a number of anti-inflammatory responses involved in malignant processes. Herein we show that B16F10 cells, a highly metastatic melanoma cell line, produce large quantities of PS-containing microvesicles in vitro. Tumor microvesicles increased TGF-b1 production by cultured macrophages and, in vivo, enhanced the metastatic potential of B16F10 cells in C57BL/6 mice, both effects being reversed by annexin V. Most strikingly, microvesicles induced melanoma metastasis in BALB/c mice, which are normally resistant to this tumor cell line. Altogether, this is the first demonstration that tumor derived microvesicles favor the establishment of melanoma metastasis in a PS-dependent manner, possibly by down-regulating the host’s inflammatory and/or anti-tumoral immune responses.

v

Title: Re: Could this be the holy grail ?
Post by: veritas on May 02, 2009, 05:50:57 am


CHAVI updates their research:

https://chavi.org/modules/chavi_reports/index.php?id=30


v
Title: Re: Could this be the holy grail ?
Post by: Inchlingblue on May 02, 2009, 12:14:44 pm
From the link above:

"Following the failure of the STEP Trial in 2008, this year has been an affirmation of the original mandate for the Center for HIV/AIDS Vaccine Immunology (CHAVI) that was to perform the basic and translational research to promote the development of a safe and effective preventive HIV-1 vaccine"

So their mandate is specifically the development of a preventive vaccine not a therapeutic one?
Title: Re: Could this be the holy grail ?
Post by: veritas on May 02, 2009, 02:55:17 pm
Inch,

The absolute way to end the hiv pandemic is to have a preventative vaccine, so yes, their mandate is to find a preventative vaccine. However, what if the vaccine was both a preventative and a therapeutic?

From the above link: 

New discoveries and progress of the B Cell Discovery Team include:

• Completed enrollement in CHAVI 005 protocol of study of protective antibodies in autoimmune diseases and defined a class of anti-lipid antibodies with breadth of protection the in vitro PBMC assay for R5 transmitted/founder strains (Nature Medicine, submitted 2009)

http://chavi.org/modules/chavi_reports/index.php?id=30

The above jumped out at me.

v

ps: I have a feeling a lot of hiv info will be coming out soon from CHAVI.
Title: Re: Could this be the holy grail ?
Post by: Inchlingblue on May 02, 2009, 04:08:37 pm
Inch,

The absolute way to end the hiv pandemic is to have a preventative vaccine, so yes, their mandate is to find a preventative vaccine. 

Believe me, I have nothing against a preventive vaccine, it would be amazing, I just did not realize that their mandate was specifically that. I thought they were also working specifically on therapeutic vaccines (and, yes, some of the vaccine candidates have potential to act as both, which is a consolation).

Not to get into a debate about it, because it's academic at this point, but I do think a therapeutic vaccine, one that essentially conferred a functional cure, would also end the HIV pandemic.
Title: Re: Could this be the holy grail ?
Post by: veritas on May 04, 2009, 03:41:30 pm

Lets follow what CHAVI been doing with lipid mabs:


FROM HAYNES’ 5-1-09 CHAVI UPDATE:
“…The (CHAVI) B Cell Discovery Team has defined a class of anti-lipid antibodies with breadth of protection in vitro PBMC assay for R5 transmitted/founder strains. (Nature Medicine, submitted 2009)”

INTERESTING:
“Acute HIV infection almost always involves virus that homes to the CCR5 coreceptor ("R5-tropic virus"). During advanced HIV disease the viral swarm may shift its focus to the alternate CXCR4 receptor ("X4-tropic virus"), but that happens in only about half of people with advanced disease.”
http://www.natap.org/2005/Euro/euro_4.htm

FROM THE HAYNES/MOODY AIDS-VACCINE’08/CAPETOWN PRESENTATION:
“We studied a panel of human anti-lipid mAbs from autoimmune disease patients & healthy controls. Mabs IS4, CL1, P1, and PGN632 bind cardiolipin and PS indep. of B2GP1… In PBMC, …B2GP1-indep. anti-lipid mAbs (PGN632, P1, IS4, CL1) inhibited HIV-1 primary isolate infection of PBMC… The most potent mAb, PGN632 [aka “11.31”], inhibited 7/7 B & C clade HIV-1 isolates and SHIV-SP162P3.
CONCLUSION: Anti-lipid human mAbs inhibit HIV-1 infection in vitro in PBMC likely by binding CD4þ T cell lipid rafts. Testing these mAbs in passive therapy trials in vivo in non-human primates will be important to determine their protective effect. Nonpathogenic anti-lipid antibodies may provide a target for HIV-1 vaccine development.
PAGE 57, #OA03-06: http://tinyurl.com/7dnmpe

FROM THE 1-6-09 NIAID REVIEW OF THE MOODY/HAYNES AIDS’08 TALK:
“NEUTRALIZING ANTIBODIES TO THWART HIV”
Tony Moody of Duke Univ. School of Medicine established a panel of B2GP1 indep. anti-lipid mabs from auto-immune disease patients. These antibodies failed to neutralize HIV in the standardized TZM-bl reporter cell line assay. However, they neutralized virus in the PBMC assay, apparently through release of b-chemokines (MIP1a, MIP1b) by monocytes in the culture. Such chemokines interfere with virus entry through the CCR5 receptor. Furthermore, neutralization could be reverted by antibodies against MIP1a and MIP1b. These anti-lipid antibodies stick to the host target cell and not the virus to prevent infection. A vaccine that induces such antibodies may not be able to directly neutralize HIV but it may reduce virus spreading.
http://www3.niaid.nih.gov/topics/HIVAIDS/Research/vaccines/reports/aidsvac2008.htm

I think its happening.

v

Title: Re: Could this be the holy grail ?
Post by: veritas on May 05, 2009, 05:42:47 am

Anti-ps will be presented at ASCO:

ASCO’09 Ph.2 Bavi/BREAST-GA: Oral Presentation
Nice to see the revelation in today’s PR that updated prelim. data from the Ph.2 Bavi+Doce/BREAST trial [GA.] was selected to be given at ASCO’09 as an oral presentation.

SK: “…we look forward to reporting updated preliminary results from the trial at the upcoming ASCO Annual Meeting [May29-June2]."

Same moa for viral !!!

I think its happening.

v
Title: Re: Could this be the holy grail ?
Post by: veritas on May 05, 2009, 10:42:23 am

IN VIVO imaging using anti-ps for cancer using arsenic:

Conclusion: For the first time, a radioarsenic labelled
antibody could be studied in vivo. The PET-images show
an impressive tumor enrichment. 74As might not be the
ideal isotope for PET, because of its low positron
emission rate of 29%, but the long half-life of 17.8 days
nevertheless makes it a useful tool for the observation of
long-term pharmacokinetics

http://www.kernchemie.uni-mainz.de/downloads/jb2003/b20.pdf

v
Title: Re: Could this be the holy grail ?
Post by: veritas on May 08, 2009, 07:50:08 am

Anti-ps and cancer:

http://www.peregrineinc.com/images/stories/media/siteFiles/Anti-PS%20Technical%20Backgrounder%20-%20Oncology.pdf

Viral has same moa -------- its happening

v

ps: read the references for peer review------- Could this be the Holy Grail for cancer?
Title: Re: Could this be the holy grail ?
Post by: freewillie99 on May 08, 2009, 10:19:05 am
its happening

What's happening?
Title: Re: Could this be the holy grail ?
Post by: J220 on May 08, 2009, 12:12:49 pm
What's happening?

I think he meant the anti-ps it working, so far, and according to the latest data released by Peregrine. Didn't you read the link he provided?

I must say I'm impressed with the anti-phosphatidylserine concept...so far. If this works as an anti-cancer agent there is a very good chance this will work as an anti-hiv agent, not to mention herpes and hepatitis, as well, because the moa, as veritas stated is the same....ps exposure on the outside of cells allows whatever pathogen they are infected to escape immune suppresion by the body, If Bavituximab can tag the PS on either hiv or cancer infected cells for destruction by the immune system, this could work....can't wait for further data...
Title: Re: Could this be the holy grail ?
Post by: Inchlingblue on May 08, 2009, 12:45:54 pm
Veritas:  Is there any news on when Bavituximab will be tested specifically for its effect on HIV?

I came across this online:

"Dr. Barton Haynes, director of Duke University's Human Vaccine Institute and the Center for HIV/AIDS Vaccine Immunology (CHAVI) is currently investigating PS as a potential target for preventing HIV infection."

http://www.eurekalert.org/pub_releases/2008-11/bp-nms111808.php

I guess this is all still pre-clinical and very early stages, right? I wonder if anyone is looking at its potential therapeutic value in treating HIV not just preventing it.
Title: Re: Could this be the holy grail ?
Post by: veritas on May 08, 2009, 04:37:27 pm
Inch,

They are testing anti-ps as a therapeutic right now in the co-infection trial of Hepc/hiv.The antibody they are using is the 3g4 antibody. This clinical trial is being done by Peregrine Pharm. The antibodies that CHAVI is testing are second generation anti-ps antibodies (pgn835 and IS4 among others). The two patents posted at the very beginning of this thread will give you an understanding as to how they work and what they do. Who knows, they might have a vaccine that works as both a preventative and a therapeutic. The CHAVI group is working on both. Some day ,if you have the time, peruse this thread from the beginning. I think a lot of your questions will be answered.
Anti-ps is in phase ll clinical trials for cancer as a therapeutic, its the same moa for viral!

v
Title: Re: Could this be the holy grail ?
Post by: Inchlingblue on May 08, 2009, 05:55:51 pm
Veritas:

Thanks very much for the info., I did know about the HIV/Hep C, I guess at some point they will further explore it vis a vis only HIV.

I have perused the entire thread before and gone back a few times to review some things, it's just that because there is so much information, it's hard to retain all of it.

Thanks for keeping us up to date with this.
Title: Re: Could this be the holy grail ?
Post by: veritas on May 10, 2009, 05:47:54 am

How about a cancer vaccine utilising anti-ps?  Harvard thinks so:

http://www.wipo.int/pctdb/images1/PCT-PAGES/2008/152008/08043018/08043018.pdf

This is a long patent. Anti-ps claims can be found on page 66 of the patent claims section.

v





Title: Re: Could this be the holy grail ?
Post by: veritas on May 15, 2009, 05:18:38 am

Anti-ps at ASCO ------ Phase ll

http://www.abstract.asco.org/AbstView_65_31930.html

It's happening!

v
Title: Re: Could this be the holy grail ?
Post by: veritas on May 15, 2009, 05:33:43 am

from IAVI Report:

30 minute Tony Fauci Discussion


Dr. Anthony Fauci, NIAID Director, reviews the history and the future potential of the HIV vaccine effort.




Fauci's closing remarks, the last segment:


"Unlocking Limitless Possibilities"

"You can't hurry this. You know how they say 'you can't hurry love?' (laughs). You can't hurry fundamental basic research. You can put more resources into it, but you can't, strictly speaking, hurry it, so we're learning more and more, and at the same time people are trying other approaches.

I think even now, while we don't have all the answers, what we're learning from studying HIV is informing us in so many important ways about understanding the immune system better. I mean, we have knowledge now about the regulation of the immune system that we never would have had if we did not study HIV, and it has impact on a number of other diseases. Our ability to study viral pathogenesis and viral biology and many other viruses has been greatly enhanced by the resources that we've put into it, so we're already starting to see spin-offs. When we get the answers I think it's going to open up more doors that will help us with other diseases.

If we can- with our own capabilities, our intellect, our will, our drive, our resources - get to a situation where we can manipulate the immune system to do something that natural infection doesn't seem to be able to elicit it to do, what else can we do with the immune system? It's just, the vista is, is, is almost infinite in what you can do, so, I see this as science to solve an extraordinarily important pandemic that has major profound global health implications, at the same time as we're furthering the knowledge of the immune system and our ability to deal with the virus / immune system interaction."

http://www.youtube.com/swf/l.swf?swf=http://s.ytimg.com/yt/swf/cpb-vfl95688.swf&player_id=bqgGH7BYHvk&datatype=playlist&color1=2b405b&color2=6b8ab6&border=1&data=E32941244F8E7190&t=KD83gDBiCSEknIB--r97uXKyyWYNCJVdbS6WPcFWcSs=&sk=7cRsk_9r91b1DYAaxT3pVXMEyjMv4cutC&eurl=&BASE_YT_URL=http://www.youtube.com/

jbm/

v
Title: Re: Could this be the holy grail ?
Post by: veritas on May 15, 2009, 09:13:14 am


Anti-ps at ASCO for another cancer indication:

http://www.abstract.asco.org/AbstView_65_35230.html

It's happening!

Same moa for viral!

v
Title: Re: Could this be the holy grail ?
Post by: veritas on May 16, 2009, 04:31:11 am

IAVI and a vaccine ----


http://www.iavi.org/news-center/news-releases/Pages/world-AIDS-vaccine-day-2009.aspx


It's happening!

v
Title: Re: Could this be the holy grail ?
Post by: veritas on May 16, 2009, 05:26:36 am

http://www.ncbi.nlm.nih.gov/pubmed/19414990?ordinalpos=4&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum


CONCLUSION: There was no single anti-HIV-1 antibody specificity that was a clear correlate of immunity in controllers. Rather, for most antibody types, controllers had the same or lower levels of nAbs than viremic individuals, with the possible exception of ADCC antibodies.
Title: Re: Could this be the holy grail ?
Post by: veritas on May 16, 2009, 07:51:08 am

A new way to rapidly produce mabs:

http://www.ncbi.nlm.nih.gov/pubmed/19428587?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

This will be exceptionally helpful for a flu vaccine but any vaccine could be accelerated.

v
Title: Re: Could this be the holy grail ?
Post by: stargate12 on May 17, 2009, 02:34:39 am

Anti-ps at ASCO for another cancer indication:

http://www.abstract.asco.org/AbstView_65_35230.html

It's happening!

Same moa for viral!

v


Please.. would you be so kind to explain better ? Bavituximab could be a cure or not ?
And if you believe that bavituximab could be a hiv cure,  why  they are still testing it for cancer and not for HIV ?
Title: Re: Could this be the holy grail ?
Post by: veritas on May 17, 2009, 08:37:49 am

stargate12,

The short answer to your question is: Bavituximab is being tested for HIV in a co-infection trial for HEPC/HIV  right now. The antibody being used is the first generation anti-ps mab. CHAVI is testing second generation anti-ps mabs specifically for HIV, both as part of a vaccine and a therapeutic.

To fully understand the concept please read the entire thread. I realise the thread is long and there is a lot of information to digest, however, by following the entire thread you should fully understand the potential of anti-ps therapy and its development.

I purposely try  to report just the facts through studies and publications so that anyone reading can come to their own conclusions based on the scientific studies and peer reviews to date. As with any therapeutic development, the science must be proven. My beliefs are just that, my beliefs. You must come to your own conclusions. However, I would not spend this much time developing this thread, if I didn't think there was cause for real hope with this therapy.


Time will tell !

v
Title: Re: Could this be the holy grail ?
Post by: veritas on May 17, 2009, 09:04:00 am

Fauci speaking  on vaccines and other needful things !

http://www3.niaid.nih.gov/about/directors/news/hvad_09.htm


While extremely rare, some individuals do develop antibodies that effectively neutralize HIV, but investigational vaccines so far have not induced these antibodies in a large number of people[b/].

Recognizing these challenges and working to build upon disappointing clinical trial outcomes, NIAID in 2008 hosted a scientific summit where we committed to placing a greater emphasis on the fundamental research needed to unlock the mysteries of the human immune system and HIV infection. Since that time, we have launched several basic research-focused initiatives and studies that are beginning to produce interesting insights that may help us design future HIV vaccines[b/]. At the same time, we continue to test promising vaccine candidates in clinical trials when scientifically appropriate.


Although vaccines will continue to play a prominent role in NIAID’s broad and multifaceted HIV prevention research agenda, other new prevention approaches are in advanced testing. These include microbicide gels or creams that can be applied prior to sexual intercourse, and pre-exposure prophylaxis—the use of antiretroviral medicines in people who are not infected with HIV but who are at high risk for infection


v
Title: Re: Could this be the holy grail ?
Post by: veritas on May 17, 2009, 09:45:23 am

More World AIDS Vaccine Day from IAVI :



"The greatest scientific challenge impeding AIDS vaccine development is the antibody problem: how to design a vaccine that elicits antibodies that neutralize the many types of HIV in circulation so that the vaccinee is protected from infection. But here, too, there is progress to report. Scientists have identified new antibodies capable of neutralizing a wide spectrum of HIV types circulating worldwide. These antibodies may now provide the keys to new vulnerable targets on the surface of HIV, which can be exploited for vaccine design"

http://www.iavi.org/news-center/news-releases/Pages/world-AIDS-vaccine-day-2009.aspx

Its Happening!

v

Title: Re: Could this be the holy grail ?
Post by: Mimi on May 17, 2009, 09:26:12 pm
What kind of vaccine are we talking about?  Therapeutic or preventative?
Title: Re: Could this be the holy grail ?
Post by: veritas on May 18, 2009, 03:57:26 am

Potentially, both. Please read the entire thread for a full overview as to the potential of anti-ps.
Title: Re: Could this be the holy grail ?
Post by: veritas on May 19, 2009, 09:49:22 am

Look at what is going to be discussed at the HIV Acute Infection Meeting in Boston this Sept:



http://www.blsmeetings.net/hivacute/TOD.cfm

It's Happening!


v
Title: Re: Could this be the holy grail ?
Post by: carpediem98 on May 19, 2009, 05:44:10 pm
Hey Veritas!

How goes it!

Would you mind clarifying which topic on the agenda is most exciting, as it pertains to anti-PS?  I've been in a bit of a haze today, so perhaps I'm just being dense... but it wasn't clear to me.
Title: Re: Could this be the holy grail ?
Post by: veritas on May 20, 2009, 04:39:21 am

carpediem98,

 5,6,7  ---------  no haze, now that I look at it , the post was  a little vague. Thanks for pointing it out.

v
Title: Re: Could this be the holy grail ?
Post by: veritas on May 20, 2009, 05:10:39 am

Remember this article concerning antibodies having trouble attaching to HIV?:


http://mr.caltech.edu/press_releases/13252

Anti-ps mabs don't have that problem:



May 19, 2009
No Need for Ab Stretches


Antibodies (Ab's) are Y-shaped molecules with two arms that can bind to a target, and one that can perform signaling functions to other immune cells. Antibodies are more potent when both of their binding arms stick to their target.

In work published last month, in the online early edition of the Proceedings of the National Academy of Sciences (PNAS), researchers discuss data showing that the parts of HIV (which poke out through the host-cell derived tag-along lipids taken from the original infected cell and which end up coating the outer surface of the virus) may be physically too far apart for antibodies to bind with both their arms, resulting in a weakened antibody response.

Lori Oliwenstein wrote a review of the work, found here:
Caltech scientists show why anti-HIV antibodies are ineffective at blocking infection "Findings provide possible explanation for failure of decades-long AIDS vaccine search"


With the Caltech discovery in mind, it's important to note the fundamental difference of a lipid-targeting approach to virus neutralization.

Until quite recently, attempts by scientists to develop powerful neutralizing antibodies against viruses were always aiming at the virus, which of course seems logical...

BUT -

Rather than targeting the traditional common-sense target of the virus spikes poking up through the host-cell lipid goop, anti-lipid antibodies do not aim for the viral spikes or anything directly to do with viral proteins at all.


Anti-lipid antibodies target the goop.

There's no need for antibody stretches. That "goop" is made up of lipids from our own cell membranes which get stuck to the virus as it exits one of our cells. It was traditionally considered a waste of time, or possibly worse, to deliberately target our own plasma membrane lipids with antibodies. That opinion is quickly changing.
(see also: "Anti-lipid Antibodies Trigger Cells to Secrete Natural HIV "Entry-Inhibitors")

It turns out that our own lipids that cling to viruses play an important role in the ability of viruses to suppress our immune response, as well as an active role in viral entry into cells, so targeting them may be a very good idea.


JBM/


It's Happening!


v
Title: Re: Could this be the holy grail ?
Post by: carpediem98 on May 20, 2009, 03:48:09 pm
Ah, yes... it looked to me like any of those could be the one you were talking about, so I wasn't sure which one... when in fact, it was all three!  :)

I must say, I am getting a bit impatient for them to start some trials of anti-PS specifically for HIV treatment!  Of course, given the alternative - a round of failure followed by potential abandonment of the whole underlying principle when it comes to willing sources of funding - waiting for them to do it properly is preferable!
Title: Re: Could this be the holy grail ?
Post by: veritas on May 21, 2009, 02:28:12 pm

Who said antibodies wouldn't be the right fit for HIV?  Anti-ps antibodies are. New abstract from CHAVI.

http://jvi.asm.org/cgi/content/abstract/JVI.00656-09v1

"We conclude that FcRI and FcRIIb facilitate antibody-mediated neutralization of HIV-1 by a mechanism that is dependent on the Fc region, IgG subclass and epitope specificity of antibody. The FcR effects seen here suggests that the MPER of gp41 could have greater value for vaccines than previously recognized."

v
Title: Re: Could this be the holy grail ?
Post by: Inchlingblue on May 21, 2009, 02:46:17 pm
Interesting...I just started a thread about IvIG (intravenous immunoglobulin) and the possibility that it aids (no pun intended) in depleting reservoirs.
Title: Re: Could this be the holy grail ?
Post by: carpediem98 on May 21, 2009, 04:57:41 pm
A question, and this will betray a chunk of ignorance I apparently am carrying regarding immune function.  So, when they begin trials specifically testing anti-PS against HIV in patients, will it first be necessary for patients to have a strong immune system so that the body CAN attack the cells that are revealed to be infected?  In that case, I wonder if what we'll see is that anti-PS works all on its own for those who discover they have HIV early on in the disease progression - but that for those who have an advanced case of the disease, that a round of HAART or HAART+Anti-PS is necessary to halt replication enough for the immune system to recover enough to self-mediate.

As I noted before - I'm impatient for them to get to the point where they can start the clinical trials in humans specifically for HIV!  (I'd rush to join!)
Title: Re: Could this be the holy grail ?
Post by: Structure310 on May 21, 2009, 07:12:03 pm
I was wondering, how would this be more effective at attaching to and binding to HIV hidden in reservoirs than current HAART medication?
Title: Re: Could this be the holy grail ?
Post by: carpediem98 on May 21, 2009, 07:50:07 pm
Hi Structure310!

Veritas might have a better handle on the science than I do, but my understanding of the principle is this.  HAART doesn't impact resting cells containing HIV because every drug involved in HAART acts directly against a specific activity of the virus - the virus is going to copy its RNA, or it's going to insert a double-stranded DNA into that of a host cell, or it's going to chop up a strand of DNA to begin budding, etc.  HAART directly intervenes, and if the cell is resting, HIV can't be interrupted while it tries to do any of those things because it isn't trying to do any of those things.

Anti-PS, howerver, doesn't act against an active virus, but against a compound on the outside of any cell containing a viral particle, whether it's "awake" or "asleep."  The reason for this would be that the cell begins to show signs of damage once it is compromised by the virus's entry.  At that point, the phosphatidylserene (PS) flips and is on the outside, and the cell appears to the rest of the immune system to be a normally dying cell rather than an infected, otherwise "normal" cell.

It might take repeat dosings to get it into all the nooks and crannies of the body, but eventually - theoretically - the anti-PS drug will have coursed throughout the body, and as it goes along, it will encounter these resting cells along with all the active, infected cells.  The resting cells, when they "wake up," will enter the bloodstream already marked for deletion as an "unwelcome invader."  HIV will not have a chance to replicate because the cell will be marked for destruction immediately upon waking up.  Theoretically, then, anti-PS has the POTENTIAL to be a treatment that would eradicate HIV as anything but a harmless, resting passenger.

How'd I do, veritas?  ;)
Title: Re: Could this be the holy grail ?
Post by: veritas on May 22, 2009, 05:32:43 am

carpediem98,

Are you trying for a Nobel Prize in anti-ps? Your explanation is spot on! The only addition, if I may, is that theoretically, the resting infected cells would  be marked for elimination in place . The immune system would destroy both the infected cells and the virus within. However, you are correct, in that should the virus breakout of an infected cell it would be marked for elimination.

You "get it " carpe, BRAVO! Now you understand why I am so excited about this therapy.

Couple your explanation with the fantastic results thus far in the cancer trials ,gives me more hope for this therapy than any other out there. The MOA (method of action) of anti-ps therapy is the same for both cancer and viral.

If all of the above isn't enough. the safety data has been TOPLINE in every clinical trial to date using anti-ps ------ NO ADVERSE EVENTS !
If the former still isn't enough, in animal trials anti-ps taught their immune system to do this on it's own so upon re-challenge with virus, their immune systems were able to fight off the virus without further dosing (ADAPTIVE IMMUNITY)!
Now you know why I ask: COULD THIS BE THE HOLY GRAIL?

v
Title: Re: Could this be the holy grail ?
Post by: veritas on May 22, 2009, 05:35:20 am

One step closer:


http://www.bmedreport.com/archives/3401

v
Title: Re: Could this be the holy grail ?
Post by: Inchlingblue on May 22, 2009, 12:25:03 pm
I didn't realize anti-ps has the potential to get at all the reservoirs, which is what it sounds like based on carpediem's explanation above.
Title: Re: Could this be the holy grail ?
Post by: veritas on May 22, 2009, 02:52:02 pm

Inch,

All cells infected with the virus expose ps, thus making them vulnerable to anti-ps therapy.  The trick is to mount a sufficient immune response to get them all.

v
Title: Re: Could this be the holy grail ?
Post by: carpediem98 on May 23, 2009, 03:50:09 am
Thanks Veritas, for both the compliment and the clarification.  :)

It would make sense that it would target "resting" cells, too - since the target is the exposed PS, not the activity of the cell.  Similarly, when an infected cell survives long enough to allow HIV to reproduce, it makes sense that as it "buds," the virus will get some PS gloop on it, so to speak.

Title: Re: Could this be the holy grail ?
Post by: xman on May 25, 2009, 01:18:10 pm
all this sounds very interesting but how long it will take to have something available for everyone? i mean how many trials are currently done? if we aren't close to at least a phase 2 clinical trial it could take decades for having the chance to get it.

the problem is that too much time is passing before we have access to a potent therapy like this.
Title: Re: Could this be the holy grail ?
Post by: Structure310 on May 25, 2009, 06:52:04 pm
Thanks Veritas and Carpe! Sounds promising.
Title: Re: Could this be the holy grail ?
Post by: xman on May 26, 2009, 01:31:04 pm
i sent an email to peregrine a couple of weeks ago to know if they plan some trials specifically for hiv. no response from them yet....
Title: Re: Could this be the holy grail ?
Post by: Inchlingblue on May 26, 2009, 04:57:53 pm
i sent an email to peregrine a couple of weeks ago to know if they plan some trials specifically for hiv. no response from them yet....

Interesting.......keep us posted if you get a response ;)

Thanks
Title: Re: Could this be the holy grail ?
Post by: xman on May 26, 2009, 05:48:49 pm
Interesting.......keep us posted if you get a response ;)

Thanks

yes i will but i feel that the response will never arrive.
Title: Re: Could this be the holy grail ?
Post by: xman on May 26, 2009, 06:01:56 pm
Second message sent a minute ago:

This is my second attempt in the hope to receive soon a response from you. I'm a bit disappointed that my first message didn't get a reply. There's plenty of folks that needs an answer on the trials involving your new drug bavituximab and HIV. We need to know at which point we are now and how many years it will take to benefit from this product. Please find the time to answer this mail.

You can contact them through the contact us form or sending a message at the following mail address:
pr@peregrineinc.com

Please try to contact them and ask for the trials involving HIV and bavituximab. Maybe if more persons are interested they will answer.
Title: Re: Could this be the holy grail ?
Post by: xman on May 26, 2009, 06:04:39 pm
On the following page you can clearly see that the HCV/HIV trial is ongoing and still in phase 1:

http://www.peregrineinc.com/index.php?option=com_content&task=view&id=20&Itemid=36
Title: Re: Could this be the holy grail ?
Post by: veritas on May 27, 2009, 09:08:10 am

xman,
I applaud your interest in anti-ps and its potential, however, I also feel your sense of urgency in your postings. Unfortunately, we cannot rush science. If you look at the link you provided to Peregrine's anti-viral program, you will notice that all trials were geared to HCV with(as you mentioned) a phase 1 combo trial with HIV. The reason why Peregrine has not started any HIV trials is due to their partnership with CHAVI (Commitee for HIV AIDS Initiative). CHAVI is doing the research for HIV using anti-ps therapy and any trials directly linked to HIV using anti-ps will come from the CHAVI group. Peregrine could not afford to do all the research that their getting from CHAVI on their own. Also, CHAVI is using second generation anti-ps mabs in their research which are stronger than those being tested in the co-infection trial. CHAVI is the group going for the homerun with anti-ps. When you have the time, please read the entire thread. I know there is a lot of information here, however, I believe it will give you a nice overview
with respect to anti-ps development.
I agree that you will probably not get a response from Peregrine with respect to your inquiry( I hope I'm wrong) because they cannot report any progress in HIV without CHAVI's ok.
I do not agree that it will take a decade to see this therapy. Development might be faster then you think (ie: it could qualify for fast-track).
CHAVI will report when they have dotted every i and crossed every t, so the information they provide you  can be confident about.
AND yes ,we DO need a cure. Enough is enough!

v
Title: Re: Could this be the holy grail ?
Post by: steppenwolf on May 27, 2009, 10:30:22 am
Hi veritas, I have been following this for a while, thank you for your research, updates and smart moderation.
This bit from CHAVI might be in the thread already, but just to follow up on who is doing what where.

(at: https://chavi.org/modules/chavi_cores/index.php?id=1)


Monoclonal Antibody Core

The Monoclonal Antibody Core is led by Dr. Barton Haynes at Duke University and Dr. James Robinson at Tulane University.  This core is responsible for producing and purifying human and mouse monoclonal antibodies (Mabs) for HIV-1 neutralization and structural studies.  The Duke team, which includes Dr. Kwan-Ki Hwang, is working to generate antibodies derived from terminal ileum (INT), bone marrow (BMA), and peripheral blood (PBL) specimens from AHI patients as part of the Antibodyome Project.  The Tulane team constructs secondary hybridomas from selected EBV transformed cells to improve antibody production and maintains a repository of purified human and mouse MAbs, EBV transformed B cell lines, and hybridomas for CHAVI investigators.

Title: Re: Could this be the holy grail ?
Post by: veritas on May 27, 2009, 05:25:20 pm

steppenwolf,

Your more than welcome. Let's hope anti-ps takes us "ON A MAGIC CARPET RIDE"!

Thanks for posting the link.

By the way, anti-ps will be discussed in an oral presentation at ASCO with only partial phase ll data from the cancer trial. Having an oral presentation with limited data at ASCO is quite an accomplishment at such a prestigious gathering of oncologists.

http://finance.yahoo.com/news/Clinical-Data-on-Peregrines-prnews-15356791.html?.v=1

IT'S HAPPENING!!

v
Title: Re: Could this be the holy grail ?
Post by: LEX40515 on May 27, 2009, 08:42:21 pm
All, is there anything we can do to help get these drugs fast tracked or is it simply a matter of process?
I find my self wishing I were a guinea pig after reading all of the great results.
Bring it on!
Title: Re: Could this be the holy grail ?
Post by: steppenwolf on May 28, 2009, 12:12:00 pm
steppenwolf,

Your more than welcome. Let's hope anti-ps takes us "ON A MAGIC CARPET RIDE"!

Thanks for posting the link.

By the way, anti-ps will be discussed in an oral presentation at ASCO with only partial phase ll data from the cancer trial. Having an oral presentation with limited data at ASCO is quite an accomplishment at such a prestigious gathering of oncologists.

http://finance.yahoo.com/news/Clinical-Data-on-Peregrines-prnews-15356791.html?.v=1

IT'S HAPPENING!!

v


Want to know something funny? I have never bought stocks before. About a week ago after reading this I wanted to try just for the heck of it and maybe for good luck. Got an account online, linked my bank...yesterday I transfered funds and checked Peregrine (PPHM), it was around $0.60, today I could finally buy my 500 bucks.....and the price jumped 63%!!! It opened at 0.80,
it's now around a dollar. After the latest news on their brain cancer drug, see below. Damn.
Oh well. I still bought.
Now we wait for their report/results on June 1st.

Go Mabs.

Steppenwolf



http://www.drugs.com/clinical_trials/peregrine-pharmaceuticals-reports-progress-cotara-brain-cancer-clinical-program-7311.html
Title: Re: Could this be the holy grail ?
Post by: steppenwolf on May 28, 2009, 12:21:24 pm
previous linked page is bad, this is better:

http://finance.yahoo.com/news/Peregrine-Pharmaceuticals-prnews-15367723.html?.v=1
Title: Re: Could this be the holy grail ?
Post by: veritas on May 28, 2009, 01:38:17 pm

steppenwolf,

Just to clarify, cotara for Gliobastoma (brain cancer) is not an anti-ps antibody. It's a targeting antibody that goes after the dead or dying cells in the center of a tumor using radioactive isotopes. It kills the tumor from the inside out and since it targets the exposed DNA histones from the dead cells, very little damage is done to the healthy brain cells. A completely different therapy from anti-ps.

v
Title: Re: Could this be the holy grail ?
Post by: steppenwolf on May 28, 2009, 01:53:10 pm
Yes thank you, I read about it and it's amazing how these drugs have multiple mechanisms and targets. I am just as happy for the brain cancer people.

steppenwolf,

Just to clarify, cotara for Gliobastoma (brain cancer) is not an anti-ps antibody. It's a targeting antibody that goes after the dead or dying cells in the center of a tumor using radioactive isotopes. It kills the tumor from the inside out and since it targets the exposed DNA histones from the dead cells, very little damage is done to the healthy brain cells. A completely different therapy from anti-ps.

v
Title: Re: Could this be the holy grail ?
Post by: veritas on May 30, 2009, 04:26:51 am

Another target for anti-ps? How about parasites? You betcha!

http://www.plosone.org/article/info:doi%2F10.1371%2Fjournal.pone.0005733

It's Happening!

v
Title: Re: Could this be the holy grail ?
Post by: veritas on June 01, 2009, 09:15:41 am

Interim data presented at ASCO shows a 71% objective tumor response to anti-ps therapy. AMAZING!
They have not completed the dosing for the trial:

http://finance.yahoo.com/news/Peregrine-Pharmaceuticals-prnews-15397810.html?.v=1


IT'S HAPPENING !!!!!!    Same moa for viral!

v
Title: Re: Could this be the holy grail ?
Post by: veritas on June 03, 2009, 08:25:08 am

Anti-ps --------- Cancer's nemisis (any cancer):

http://finance.yahoo.com/news/Peregrine-Pharmaceuticals-prnews-15423221.html?.v=1

Same MOA for viral! It's Happening!

v
Title: Re: Could this be the holy grail ?
Post by: sensual1973 on June 03, 2009, 12:55:27 pm
is this ps things being tested on people living with HIV ?
or are we just jerking off to get through the day ?
Title: Re: Could this be the holy grail ?
Post by: veritas on June 03, 2009, 04:24:09 pm

is this ps things being tested on people living with HIV ?
or are we just jerking off to get through the day ?

I don't know if your jerking off to get through the day, but the answer to your first question has been answered many times in this thread.

v
Title: Re: Could this be the holy grail ?
Post by: simpleguy on June 05, 2009, 04:13:27 am
sensual1973, I'm beginning to suspect veritas might have bought stocks in Peregrine Pharma :D :D

HIV + Hep C clinical trial, bavituximab: http://clinicaltrials.gov/ct2/show/NCT00503347 (http://clinicaltrials.gov/ct2/show/NCT00503347)
Results expected by the end of 2009 (it says september, but who knows...)

Anti-PS explained in layman's terms (and potential investors terms ;o) can be found at
http://www.peregrineinc.com/ (http://www.peregrineinc.com/)

Cheers!
Title: Re: Could this be the holy grail ?
Post by: veritas on June 05, 2009, 06:17:47 am

simpleguy,

Both links that you posted have been posted on this thread earlier. Peregrine Pharm. is the only company doing research on anti-ps therapy in conjunction with partners. CHAVI picked anti-ps as a necessary therapy  to be studied in order to develop a vaccine and cure. If you are following anti-ps, you must follow Peregrine. If you can find another company not affiliated with Peregrine that is researching anti-ps please post (there aren't any).

As I stated before, CHAVI will be announcing clinical trils for HIV directly. The combination trial HIV/HEPC that Peregrine is running will give us an indication as to the viability for anti-ps in vivo. The mabs being used are not as powerful as the mabs CHAVI is using for HIV directly. I expect preliminary data to be released for the HEPC/HIV trial as they did for the cancer trials before Sept, when the trial is to conclude. I also expect a paper to be released from CHAVI in the near future with respect to their pre-clinical developmental research on HIV. (Look to "Nature").

I am fully convinced from my own research that anti-ps is the pathway to a breakthrough for this disease.Those are my beliefs and I have tried to back-up my beliefs with the appropriate links. YOU do not have to believe in this therapy. This thread is not required reading.However, there are many readers of this thread who are intrigued by this research as I am. I wonder if even you haven't thought about joining a clinical trial with this therapy. I hope they have one in Denmark.

The research is not on our timeline, unfortunately. If I could influence a faster development I would. So we wait. Read or don't read----it's up to you.

v


Title: Re: Could this be the holy grail ?
Post by: simpleguy on June 05, 2009, 06:47:12 am
veritas,

I respect your enthusiasm and the work you do for posting news about anti-ps in this thread. I believe when I see the results of the research and trials. Until then I will keep my feet on the ground and just follow the news about the anti-ps research.

Cheers!  :)
Title: Re: Could this be the holy grail ?
Post by: veritas on June 05, 2009, 08:59:44 am


simpleguy,

How's your Latin?


Libenter homines id quod volunt credunt !(LOL)

v
Title: Re: Could this be the holy grail ?
Post by: xman on June 05, 2009, 12:53:03 pm
The research is not on our timeline, unfortunately.

Do you mean that we will unlikely benefit from the results in our lifetime?
Title: Re: Could this be the holy grail ?
Post by: freewillie99 on June 05, 2009, 01:15:55 pm
Do you mean that we will unlikely benefit from the results in our lifetime?

Heh...what a creative interpretation.  Pessimism much?
Title: Re: Could this be the holy grail ?
Post by: mpositive on June 05, 2009, 01:35:17 pm
blah blah blah blah.....hey, all of you, keep up the great work.  your opinions matter, your links to all this research matters and your comments matter...at to me who does none of this on my own and rely on good folks like yourselves. 
So.....seriously, thanks for all this.....and I mean all of it, the positive and negative is all valuable in it's way.

:)
Title: Re: Could this be the holy grail ?
Post by: veritas on June 05, 2009, 02:38:22 pm
Do you mean that we will unlikely benefit from the results in our lifetime?


no

v
Title: Re: Could this be the holy grail ?
Post by: Inchlingblue on June 05, 2009, 02:46:04 pm
Do you mean that we will unlikely benefit from the results in our lifetime?

Xman: I'm pretty sure what he meant was that, since those of us with HIV have a vested interest in anything that shows promise as a possible cure (functional or otherwise), we'd prefer that these studies move along at a faster clip than they actually do, hence "the research is not on our timeline."

 
Title: Re: Could this be the holy grail ?
Post by: veritas on June 06, 2009, 09:05:29 am

What are some of the ways cells use PS? ------- more research:



http://jcb.rupress.org/cgi/content/short/185/5/917?rss=1


v
Title: Re: Could this be the holy grail ?
Post by: veritas on June 08, 2009, 12:55:59 pm

PS and the immune system:


ABOUT PHOSPHATIDYLSERINE (PS)
The rapid and disorganized growth that is the hallmark of cancer results in the exposure of the lipid phosphatidylserine (PS) on the surface of tumor blood vessels. Since these phospholipids are typically not exposed on the surface of normal tissues, they represent a unique target for anti-cancer treatments. Bavituximab binds specifically to these phospholipids exposed on the surface of the cells lining tumor blood vessels. Once bound, bavituximab alerts the body's immune system to attack the blood vessels, inhibiting tumor growth and proliferation. In addition, a growing body of evidence supports the active role of PS in immune signaling, with recent research showing that exposed PS can have an immunosuppressive effect and dampen the body's normal immune response to cancer. By binding to and blocking PS, bavituximab is believed to boost the body's ability to combat cancer via this second mechanism. Further information on the role of exposed PS in the tumor environment can be found in the Anti-PS Technical Backgrounder posted on Peregrine's homepage at http://www.peregrineinc.com.

It's Happening!

v

Title: Re: Could this be the holy grail ?
Post by: J220 on June 08, 2009, 04:37:03 pm
Hey V. have you seen the PPHM stock lately? Decent gains after the last several positive data releases. Last price today was .83. I went in back in January at .45, so as you can imagine I'm happy so far. I do think (hope) that when the trials are done this is going to go way up, maybe even double digits. That would be something. Of course if it tanks then I'll be SOL, but the data so far looks solid for this to make it to therapeutic use, probably cancer first and then maybe hiv as well. In any case...me? 'll keep buying...maybe this will cure me and also make me some decent money! lol
Title: Re: Could this be the holy grail ?
Post by: Matts on June 09, 2009, 05:02:41 am
Hello,

does anybody know if there already some results about the DTRA Research and Bavituximab?

What happened to Human Genom Sciences Mabs, they develepod also some very promising HIV Antibodies like HGS CCr5mab, HGS 101 and others, but now only focus on cancer, anthrax etc. It is the same like Medarex MD101, PD-1, Zenapax, Erbitux, Orthoclone OKT3 and others.
Is HIV so uninteresting compared to cancer, smallpox, HCV or anthrax ?:(


Affitech and Pharmexa have merged to get the leading Antibody company http://www.pharmexa.com/resources/299.pdf (http://www.pharmexa.com/resources/299.pdf)
In cooperation with Peregrine and Bavarian Nordic there will be hopefully more new promising vaccines and antibodies against HIV in the future.
Title: Re: Could this be the holy grail ?
Post by: veritas on June 09, 2009, 07:45:01 am


Here's what they are doing with HIV:

HIV: PS ligands have potently inhibited HIV from infecting
macrophages in vitro (7), suggesting a possible functional role of
PS in HIV infection. In 2005, researchers discovered that rare
antibodies found in HIV-infected patients that broadly neutralize
multiple strains of HIV share the common feature of binding to PS
and other lipids (10). Data also shows that autoimmune disease
patients with systemic lupus erythematosus (SLE) experience a
lower incidence of HIV/AIDS than would be expected in the general
population (11). This may be due to the SLE patients' ability to
produce HIV-neutralizing anti-lipid antibodies more readily than
people with normally functioning B cell tolerance mechanisms (11).
These observations are among the hypotheses underlying
approaches being assessed by Duke University’s NIH-funded
Center for HIV/AIDS Vaccine Immunology (CHAVI) which is
collaborating with other academic centers and with scientists at
Peregrine to evaluate the potential of anti-PS antibodies to broadly
neutralize HIV infection. Positive initial results from these studies
were presented at the AIDS Vaccine 2008 conference (12
v
Title: Re: Could this be the holy grail ?
Post by: xman on June 09, 2009, 01:12:30 pm
I got a response from Peregrine:

As you note, bavituximab is in a pilot study in hepatitis C (HCV) patients who are co-infected with HIV.  The focus of this study is on bavituixmab's activity against HCV, with HIV being a secondary endpoint.  The enrollment criteria for this study required by the FDA have hindered the speedy progress of the trial, so while it is proceeding, it is doing so slowly.  Peregrine will report preliminary results when it has a meaningful number of treated patients to discuss.  There are no current plans to conduct trials solely in HIV.
 
Please direct any further questions to this email address.  Peregrine's clinical staff are responsible for overseeing our eight ongoing clinical trials rather than responding to information requests, which is our job.  Thank you for you consideration.

I sincerely don't know what they mean by saying that HIV is a secondary endpoint. What is sure is that they are not interested in beginning trials only for HIV at the moment. Don't know if this is good or bad news and if we could benefit from this trial.

It seems also that the FDA has put some limitation on the trial.
Title: Re: Could this be the holy grail ?
Post by: veritas on June 10, 2009, 08:39:59 am

ASCO believes in anti-ps enough so to award a grant for futher study in lung cancer:

http://finance.yahoo.com/news/ASCO-Research-Foundation-prnews-15486939.html?.v=1

IT'S HAPPENING !!! (now, if only CHAVI would come through for HIV)

v
Title: Re: Could this be the holy grail ?
Post by: J220 on June 10, 2009, 03:26:06 pm
I got a response from Peregrine:

As you note, bavituximab is in a pilot study in hepatitis C (HCV) patients who are co-infected with HIV.  The focus of this study is on bavituixmab's activity against HCV, with HIV being a secondary endpoint.  The enrollment criteria for this study required by the FDA have hindered the speedy progress of the trial, so while it is proceeding, it is doing so slowly.  Peregrine will report preliminary results when it has a meaningful number of treated patients to discuss.  There are no current plans to conduct trials solely in HIV.
 
Please direct any further questions to this email address.  Peregrine's clinical staff are responsible for overseeing our eight ongoing clinical trials rather than responding to information requests, which is our job.  Thank you for you consideration.

I sincerely don't know what they mean by saying that HIV is a secondary endpoint. What is sure is that they are not interested in beginning trials only for HIV at the moment. Don't know if this is good or bad news and if we could benefit from this trial.

It seems also that the FDA has put some limitation on the trial.


Secondary endpoint means that they will in fact be monitoring the effects of the therapy on HIV pathogenesis. So it's all good. I would consider ourselves lucky that HIV is included in the inclusion criteria.

It's proably a matter of cost of why they went with HCV/HIV coninfection. If you do two different trials, one for HCV alone and one for HIV alone, it's double the cost, time, energy, and red tape by the FDA. So I think it's a perfect solution to do with coninfection.

In terms of Bavituximab's effect on HIV, it will probably make no difference it it's in a coninfection setting. So rest easy, this trial will answer the question of anti-PS therapy wil in fact work in vivo. Fingers crossed!!

p.s. in other news, as I stated before I bought some Peregrine stock...last check, up 11%, to $0.94....go Peregrine!
Title: Re: Could this be the holy grail ?
Post by: Inchlingblue on June 10, 2009, 03:36:49 pm
An article in Bio-Medicine dated March 20,2009 states the following, which sounds promising but wish there were more details:

Dr. Barton Haynes, director of Duke University's Human Vaccine Institute and the Center for HIV/AIDS Vaccine Immunology (CHAVI) is currently investigating PS as a potential target for preventing HIV infection. He commented, "Targeting a host cell lipid such as PS as an anti-viral strategy is an intriguing concept that may have relevance for new therapeutic and possibly prophylactic innovations in a number of virus infections."


This is actually the same article that's been reprinted everywhere since November 2008 (and is probably already on this thread). I guess they are "on it.''  **fingers crossed**

LINK:

http://www.bio-medicine.org/biology-technology-1/Nature-Medicine-study-shows-Peregrines-bavituximab-can-cure-lethal-virus-infections-11132-3/
Title: Re: Could this be the holy grail ?
Post by: J220 on June 10, 2009, 04:33:10 pm
I can fully understand the excitement about this therapy candidate.....IF it works it could cure not only HIV, but Hepatitis, even Herpes....! And treat or cure cancer to boot! Man if only this worked.....I think humanity is ready for a lucky break....let this work. The enouraging things is that so far the news from the trials look good so there is cause for optimism.
Title: Re: Could this be the holy grail ?
Post by: veritas on June 10, 2009, 05:00:40 pm
I can fully understand the excitement about this therapy candidate.....IF it works it could cure not only HIV, but Hepatitis, even Herpes....! And treat or cure cancer to boot! Man if only this worked.....I think humanity is ready for a lucky break....let this work. The enouraging things is that so far the news from the trials look good so there is cause for optimism.

J220,

Now you understand why I named this thread "Could this be the Holy Grail ?". The results of the cancer trials so far have proven the concept. The preclinicals for retroviruses have been amazing. Both Hepc and HIV are retroviruses. The MOA is the same for all. The therapy does not go after the cancer or the virus directly (resistance is futile).....it goes after the exposed ps on infected cells. It's like shining a big light on the invaders exposing them to your immune system to do it's work. The question is ...Can a strong enough immune response be generated to do the trick? That's what CHAVI is working on.

Time will tell!

v
Title: Re: Could this be the holy grail ?
Post by: veritas on June 17, 2009, 07:32:37 am

NIAD likes antibody based vaccines ----- I wonder what antibodies they like?:

http://www3.niaid.nih.gov/news/newsreleases/2009/antibody_hiv_vax.htm

I hope they tell us soon.

v
Title: Re: Could this be the holy grail ?
Post by: a2z on June 18, 2009, 08:57:17 pm
NIAD likes antibody based vaccines ----- I wonder what antibodies they like?:

http://www3.niaid.nih.gov/news/newsreleases/2009/antibody_hiv_vax.htm

I hope they tell us soon.

v

Hot, muscular antibodies with nicely tanned pecs. :)
Title: Re: Could this be the holy grail ?
Post by: veritas on June 19, 2009, 04:51:11 am

a2z,

I see they're a turn -on for you too? (Too much is not enough!) LOL!


v
Title: Re: Could this be the holy grail ?
Post by: veritas on June 19, 2009, 05:13:34 am

Does malaria use exposed ps? ------ YUP!

http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowAbstract&ArtikelNr=67908&Ausgabe=228865&ProduktNr=224332


v
Title: Re: Could this be the holy grail ?
Post by: a2z on June 20, 2009, 04:21:33 am
a2z,

I see they're a turn -on for you too? (Too much is not enough!) LOL!


v

I like several types..muscles not necessary.
Title: Re: Could this be the holy grail ?
Post by: veritas on June 24, 2009, 08:09:30 am

More good news for anti-ps and cancer:

http://finance.yahoo.com/news/Peregrine-Pharmaceuticals-prnews-2498131896.html?x=0&.v=1

v
Title: Re: Could this be the holy grail ?
Post by: xman on June 24, 2009, 06:33:28 pm
I received a second response from Peregrine a couple of weeks ago:

It is possible that the bavituximab anti-viral program could include further trials in HCV patients co-infected with HIV and potentially in other viruses in the future, but we cannot predict the indications or timing for future trials at this time (while the HCV/ HIV trial is still ongoing).  If these trials are positive, we would expect Peregrine and our shareholders ultimately to benefit.  Thank you for your interest in Peregrine.

I replied them that I'm HIV positive and not interested in the results as an investor and profitmaker but as a patient.

There's a lot of research and clinical studies ongoing but my concern is that most of them are only made with the intent to receive public and private funds without any benefit except for shareholders. This feeling is not due to the response from Peregrine which ignores completely the positive outcome for patients (this should be the most important target) but for all those incouraging news that comes out periodically about a discovery, study or compound which then quickly disappears just in time to receive the right attention for some fundings. If you go back some years you see a lot of this announcements and all are very optimistic. Where are all this products now? Trials never finished or never started. I don't know how many dollars went in those researches but it's another reason to think that most of the time and the huge amount of money get lost for nothing except for the careers of some scientists or the shareholders of those companies.
Title: Re: Could this be the holy grail ?
Post by: veritas on June 25, 2009, 08:52:56 am

xman,

Following research can be extremly frustrating, especially when one has a health problem that could possibly benefit from that research. I'm happy to see that the company answered your inquiry even though it wasn't the answer you wanted to hear. Peregrine is partnered with CHAVI for the development of a vaccine and a cure using anti-ps. Any trials for HIV directly will come from CHAVI, they are doing the HIV research directly. Again, they are not on our timeline------ they want to get it right. I understand your anxiety (and you have only been following this thread for a relatively short period of time). I have been following anti-ps since the late nineties. There were times I thought it would never get to clinical trials for any indication. Well it's finally happening. We have to wait a little longer for HIV directly, but at least they are working on it. Knashing of teeth won't help. Let the research run its' course and in the meantime try to stay as healthy as possible.

v


Title: Re: Could this be the holy grail ?
Post by: veritas on June 25, 2009, 08:56:21 am

CHAVI chugs along:

http://www.faqs.org/patents/app/20090136522

Scoll down to read, for those who are interested.

v
Title: Re: Could this be the holy grail ?
Post by: Inchlingblue on June 25, 2009, 01:29:39 pm
CHAVI chugs along:

http://www.faqs.org/patents/app/20090136522

Scoll down to read, for those who are interested.

v

Is this patent for anti-ps specifically?

If so: woo-hoo!  ;)
Title: Re: Could this be the holy grail ?
Post by: veritas on June 25, 2009, 01:40:24 pm

Inch,

It SURE IS:

[0004]Haynes et al, Science 308:1878 (2005) recently discovered that three of the rare HIV-1 broadly neutralizing antibodies (2F5, 4E10, 1b12) are polyspecific and bind to self antigens that include the anionic phospholipid, cardiolipin. Interaction of 2F5 and 4E10 mAbs with membrane lipids were also proposed in crystal structure studies that showed that the highly hydrophobic CDR3 regions of both mAbs made little contact with the peptide and were largely free (Ofek et al, J. Virol. 78:10724 (2004), Cardoso et al, Immunity 22:163 (2005)). This raises the possibility that the current vaccines fail to produce such mAbs due to their potential self-reactivity, which is regulated such that autoreactive B cells are normally deleted or tolerized against HIV-1 envelope. The present invention results at least in part, from studies designed to test this hypothesis.

v

Title: Re: Could this be the holy grail ?
Post by: brazilianman on July 06, 2009, 08:31:47 pm
hello, I'm from Brazil and I like the forum on anti-ps is a good theory. I would like to know what the strength of the forum to ask for drug companies on research? much is spoken but not proven. vrx496? pro 140? Anybody know about this? sorry bad English.


Antibody specificities associated with neutralization breadth in plasma from HIV-1 subtype C infected blood donors
Title: Re: Could this be the holy grail ?
Post by: veritas on July 07, 2009, 05:24:34 pm

How will the body fight off a HIV attack when it destroys gut antibody immune cell production?

"Then, if the virus manages to escape that first line of defense, the vaccine would need to be able to educate the immune system to rapidly respond to eliminate transmitted virus strains. It is this continually emerging picture of what happens at the very earliest period after infection that is helping us to understand the job we have to do," Haynes said.

http://www.dukehealth.org/HealthLibrary/News/hiv_1_damages_gut_antibody_producing_immune_cells_within_days_of_infection

It's Happening!

v
Title: Re: Could this be the holy grail ?
Post by: Inchlingblue on July 07, 2009, 06:08:57 pm
How will the body fight off a HIV attack when it destroys gut antibody immune cell production?

"Then, if the virus manages to escape that first line of defense, the vaccine would need to be able to educate the immune system to rapidly respond to eliminate transmitted virus strains. It is this continually emerging picture of what happens at the very earliest period after infection that is helping us to understand the job we have to do," Haynes said.

http://www.dukehealth.org/HealthLibrary/News/hiv_1_damages_gut_antibody_producing_immune_cells_within_days_of_infection

It's Happening!

v

V: Please bear with me, but I don't understand the connection between the article you cite, and the quote from Haynes and anti-ps (other than in the broadest terms).
Title: Re: Could this be the holy grail ?
Post by: veritas on July 08, 2009, 06:26:49 am

Inch,

How do you "educate" the immune system? Anti-ps antibodies shine the light!

If you want to go in-depth, here's the abstract in full ---- long read----but it's Happening!

http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1000107

Quiz: Can you connect the therapeutic value of this potential preventative vaccine?

v
Title: Re: Could this be the holy grail ?
Post by: brazilianman on July 08, 2009, 07:41:47 am
veritas,
hello , the pilgrimage already acabou phase I hepatitis c. anybody information? the two applications already have been off the rack. when será divulged? sorry bad ingles
Title: Re: Could this be the holy grail ?
Post by: veritas on July 08, 2009, 09:17:13 am

brazilianman,

I'm not quite sure what you are asking? But , if your looking for the data from the Hepc/hiv trial---- the trial should be completed around sept. Preliminary data hopefully will be released sooner. However, the trial in progress is using Bavituximab ( an anti-ps mab), it is not the vaccine that CHAVI is working on.

v
Title: Re: Could this be the holy grail ?
Post by: brazilianman on July 08, 2009, 09:56:21 am
from veritas.
sorry. my English is very bad. I speak of the stage of hepatitis C. no hepatitis C / HIV. only hepatitis c. that phase I is over. and they have not shown the reports phase I hepatitis c. I know that this drug is not a vaccine of the CHAVI. but right now if it is a good sign.
Title: Re: Could this be the holy grail ?
Post by: veritas on July 08, 2009, 10:12:05 am

Here you go brazilianman:

Positive Results From Peregrine Pharmaceuticals' Bavituximab Phase l HCV Trial Presented at AASLD Meeting
• Bavituximab Appeared Generally Safe and Well Tolerated at All Doses Tested
• Signs of Anti-viral Activity Seen at All Dose Levels
• Exploratory Analysis of Cytokine Profile Following Treatment Supports Proposed Immunomodulatory Mechanism of Action
http://www.peregrineinc.com/content.php?mi=MTc=&appAction=--PRINT&Id=MTA3MjM3Mg

v
Title: Re: Could this be the holy grail ?
Post by: brazilianman on July 08, 2009, 10:18:37 am
Hello Mr. brazilianman,
Thank you for your inquiry.  At this time our Phase 1 study in co-infected patients is ongoing.  Study results will be reported after the study has been completed.  The results will be reported at the appropriate scientific/medical meeting.
Regards,
Dianne
 
Dianne Uphoff, RN; CCRA | Sr. Clinical Project Manager
 
Peregrine Pharmaceuticals, Inc.
14282 Franklin Avenue - Tustin, California - 92780
Tel: +1.714.508.6031 | Corporate: +1.714.508.6000 | Fax: +1.714.734.1692
duphoff@peregrineinc.com | http://www.peregrineinc.com
 
Reply  brazilianman:

thanks for the reply mrs. Dianne. I know that the studies with co-infection are in progress. but only for patients with hepatitis C is already complete. so says the pipeline. sorry if I can not express right. my inglesh is very bad
Title: Re: Could this be the holy grail ?
Post by: brazilianman on July 08, 2009, 10:48:53 am
from veritas.
ok. you are right. is happening.

files.shareholder.com/.../PPHM_News_2006_10_30_General.pdf
Title: Re: Could this be the holy grail ?
Post by: brazilianman on July 09, 2009, 06:06:40 pm
news
http://www.theraclone-sciences.com/pdf/IAVI_Theraclone_070209.pdf ;D
Title: Re: Could this be the holy grail ?
Post by: veritas on July 11, 2009, 05:01:10 am

Is "Nature Medicine", the most prestigious publication for medical research, about to publish a Focus issue on HIV vaccine research? What will the new research show? Will there be any surprizes?

Stay tuned--------- ITS HAPPENING!!!!!!

http://www.nature.com/nm/journal/vaop/ncurrent/index.html

Enough is Enough---- HIV must be defeated!!!!!

v
Title: Re: Could this be the holy grail ?
Post by: Luke on July 11, 2009, 05:24:53 am
"Nature Medicine", the most prestigious publication for medical research

Excuse me, but in which parallel universe is Nature Medicine "the most prestigious publication for medical research" and more prestigious than The Lancet, The New England Journal of Medicine and the Journal of the American Medical Association?

Just wondering.
Title: Re: Could this be the holy grail ?
Post by: veritas on July 11, 2009, 05:31:16 am

Perhaps you should read it.

But lets not restart 1776.

v
Title: Re: Could this be the holy grail ?
Post by: Luke on July 11, 2009, 05:36:14 am
Perhaps you should read it.

I do, thanks

Quote
But lets not restart 1776

It has nothing to do with 1776 .. and you still haven't answered.
Title: Re: Could this be the holy grail ?
Post by: veritas on July 11, 2009, 05:42:55 am

I guess its a matter of opinion ----- please don't clutter this thread with nonsense-- v
Title: Re: Could this be the holy grail ?
Post by: Luke on July 11, 2009, 05:45:30 am
Sweetheart, you cluttered it with nonsense when you made such a banal claim. You obviously made it for a reason and I am simply asking why. The fact that you refuse to answer, and make even more banal comments about 1776, is most revealing. Thanks.
Title: Re: Could this be the holy grail ?
Post by: veritas on July 11, 2009, 06:21:11 am

For those who are not familiar with "Nature " ---- here's a link:

http://www.nature.com/nm/authors/index.html

v

Title: Re: Could this be the holy grail ?
Post by: brazilianman on July 11, 2009, 08:42:18 am
veritas

entered the link. not found. where is it?
Title: Re: Could this be the holy grail ?
Post by: veritas on July 11, 2009, 08:46:26 am

See link for some other Focuses and supplements in "Nature". The last time HIV was in Focus was in 2003.

http://www.nature.com/nm/focsup_index.html

v
Title: Re: Could this be the holy grail ?
Post by: veritas on July 11, 2009, 08:57:41 am

braziliaman,

The advance publications can be found here:

http://www.nature.com/nm/journal/vaop/ncurrent/index.html

The Focus or supplement on HIV has not been published yet --- but should be shortly.

I believe we will find it very exciting!

v
Title: Re: Could this be the holy grail ?
Post by: brazilianman on July 11, 2009, 09:33:17 am
group to know a little Portuguese

adimiro o otimismo de veritas. concordo com ele que em breve teremos novidades animadoras. mas  a demora de alguns estudos me matam de ansiedade. beijos a todos.
Title: Re: Could this be the holy grail ?
Post by: brazilianman on July 11, 2009, 09:35:31 am
from ingles

I like the optimism of veritas. I agree with him that soon we will have encouraging news. but the delay of a few studies of anxiety kill me. kisses to all.
Title: Re: Could this be the holy grail ?
Post by: veritas on July 12, 2009, 04:15:34 am

The father of ANTI-PS, Dr. Philip Thorpe,, is interviewed by "The Behavioral Medicine Report".

'Question: Where is Bavituximab with the FDA process? Should Bavituximab be “fast tracked” through the FDA process in light of the millions of people who are sick and dying from viral-based diseases?

Dr. Thorpe described two ongoing phase 1 clinical trials – one with Hepatitis C, and another with Hepatitis C and HIV. In regard to “fast-tracking” the drug, Dr. Thorpe hopes that the FDA will adopt this attitude.'

 

Question: Have you conducted additional Bavituximab studies with any of the viruses mentioned in the Nature Medicine article or with the herpes (oral/genital) and Epstein Bar (EBV) viruses?

Dr. Thorpe reported that Bavituximab has now been tested with HIV in collaboration with Dr. Barton Haynes and colleagues at Duke University Medical Center. He stated that they found that several antibodies which recognize phosphatidylserine can control HIV proliferation in cultured cells and can control multiple clades of HIV – adding that this is a very big finding. Dr. Thorpe further responded that Bavituximab has not been studied with genital or oral herpes or EBV. Also, he said that it is not known whether cells infected with viruses like these which can become latent will continue to have exposed phosphatidylserine. He went on to state that this may not matter because the current thought is that you might be able to deplete the pool of virus during the active phase of infection and if the latent pool of virus can not be replenished then it will die out.


IT'S HAPPENING !!!!!!!!


http://www.bmedreport.com/archives/4486#more-4486

v

'
Title: Re: Could this be the holy grail ?
Post by: Inchlingblue on July 12, 2009, 05:43:51 pm
Also, he said that it is not known whether cells infected with viruses like these which can become latent will continue to have exposed phosphatidylserine. He went on to state that this may not matter because the current thought is that you might be able to deplete the pool of virus during the active phase of infection and if the latent pool of virus can not be replenished then it will die out.


I guess this particular statement is referring to herpes and Epstein Barr and not HIV?
Title: Re: Could this be the holy grail ?
Post by: veritas on July 13, 2009, 04:37:00 am

Inch,

He doesn't distinguish because it has not been proven (yet) in clinical trials. He has to be careful what he says until he has the evidence in hand. But he softens the statement with "that this may not matter"
quote. He seems to be setting it up as a either/or ---- its a win/win.

IT's Happening Inch!

v
Title: Re: Could this be the holy grail ?
Post by: Inchlingblue on July 13, 2009, 12:11:08 pm
Of course more research is needed to answer many questions, but if they are saying that anti-ps may only work at depleting latent virus during the acute phase of infection then it would rule out using it as a therapeutic or possible functional cure for HIV for those many of us past the acute phase.

But I'm still hopeful and look forward to seeing the results of the HepC/HIV study, which I'll trust you'll post here as soon as you find out about it ;)
Title: Re: Could this be the holy grail ?
Post by: veritas on July 13, 2009, 12:48:46 pm

Inch,

My quote was only referring to that part of the interview dealing with latent viral infected cells.

Didn't you read this?:

Question: Can you tell me more about Bavituximab?

Dr. Thorpe explained that Bavituximab is an antibody – or more concisely a protein produced by the immune system – that binds to a flipped cellular phospholipid, called phosphatidylserine. He went on to state that when cells are activated or stressed they expose their phosphatidylserine. This occurs on cells that line blood vessels inside tumors and on virally infected cells. Bavituximab binds to the phosphatidylserine and helps the immune system recognize the diseased cells. These actions then trigger an immune system response that clears the virally infected cells and their infectious virions. Dr. Thorpe’s study further demonstrates that the addition of traditional anti-viral drugs further facilitates the removal of these viruses, at least in guinea pigs and mice.

THATS THERAPEUTIC!!  By the way, its also the answer to the Quiz question in an earlier post.

v
Title: Re: Could this be the holy grail ?
Post by: Inchlingblue on July 13, 2009, 01:03:50 pm
I was wondering about that quiz question ;)

I was not sure how anti-ps would work with the HIV in reservoirs, which is what I was trying to figure out I guess. In the interview he says

Question: Do all latent viruses trigger exposure of phosphatidylserine?

Dr. Thorpe stated that the active (i.e., viral replication) phase always appears to triggers exposure of phosphatidylserine, but that it is currently unknown whether cells in which the virus has become dormant, or ‘latent’, will continue to have exposed phosphatidylserine.

So I guess the current thinking is that anti-ps would be used along with HAART? It seems at this point it's still speculative as far as how specifically it would work since it's not known if latent HIV would trigger exposure of ps.
Title: Re: Could this be the holy grail ?
Post by: veritas on July 13, 2009, 01:11:16 pm

Inch,

Don't come to any conclusions yet. Remember, CHAVI is working with much more powerful anti-ps mabs than  the 3g4 antibody being used in the clinical trial.  I believe we will be pleasantly surprised!

It's Happening !!

v
Title: Re: Could this be the holy grail ?
Post by: brazilianman on July 13, 2009, 01:54:47 pm
veritas I thought about adverse effects or toxicity of bavituximab.
and toxic?
Title: Re: Could this be the holy grail ?
Post by: veritas on July 13, 2009, 04:59:54 pm

braziliaman,

The safety data from all the trials thus far has been top-line.
Minimal  adverse reactions.
v
Title: Re: Could this be the holy grail ?
Post by: veritas on July 14, 2009, 08:09:29 am


Bavituximab Anti-Viral Program

The company continued to advance the bavituximab anti-viral program:

    --  Received major validation of the broad anti-viral potential of the
        company's anti-PS antibody platform with the publication of data in
        Nature Medicine showing that its PS-targeting drug bavituximab can cure
        lethal virus infections in animal disease models.
    --  Entered into a five-year contract potentially worth up to $44.4 million
        with the Department of Defense's Defense Threat Reduction Agency
        (DTRA), and ramped up activities under this contract to assess
        bavituximab and other anti-PS antibodies for biodefense applications
        against viral hemorrhagic fevers.
    --  Continued to enroll and dose patients in an ongoing Phase I clinical
        trial of bavituximab in hepatitis C virus infected patients co-infected
        with HIV.
    --  Was awarded a U.S. patent that includes broad claims covering anti-viral
        applications of antibodies that directly bind to aminophospholipids,
        including PS.

    --  Reported that the company's anti-PS technology was positively
        highlighted in scientific sessions at the AIDS Vaccine 2008 conference
        in Cape Town, South Africa.

http://www.peregrineinc.com/index.php?option=com_frontpage&Itemid=1

ITS HAPPENING!!!

v
Title: Re: Could this be the holy grail ?
Post by: brazilianman on July 15, 2009, 10:16:16 am
veritas
 was not about HIV or focus. was on obesity.


http://links.ealert.nature.com/ctt?kn=7&m=33607722&r=Mjg4NzcyODc0NAS2&b=2&j=NTMyMTE1NjQS1&mt=1&rt=0
Title: Re: Could this be the holy grail ?
Post by: veritas on July 15, 2009, 05:02:57 pm
braziliaman,

The FOCUS paper on hiv has not been published yet.

v
Title: Re: Could this be the holy grail ?
Post by: elf on July 20, 2009, 06:25:19 pm
Oi brazilianman, como a gente pode ajudar você?
A gente não tem nenhuma influência no âmbito de pesquisas, infelizmente.  :'(
As pesquisas vão pingando, pros cientistas é quase um hobby, e pra nós que esperamos,
uma coisa muito séria...Se eles tivessem um prazo, logo logo achariam a cura definitiva...(tipo, se os et's falassem: achem uma cura em 5 anos ou vamos acabar com sua raça)...Infelizmente, deveria ter mais dindim à disposição, os laboratórios recebem pouca grana. E não tem interesse dos governos...Baita pena. :(

um baita beijo, a kiss from Europe
Title: Re: Could this be the holy grail ?
Post by: veritas on July 21, 2009, 04:57:51 am

elf,

Please translate the above post for the benefit of all.

Thanks,

v
Title: Re: Could this be the holy grail ?
Post by: Matts on July 21, 2009, 05:43:01 am
B. Haynes patent on using different Mabs; PS/PE against HIV:
(WO/2009/025864) "METHODS OF TREATING AND PROTECTING AGAINST HUMAN IMMUNODEFICIENCY VIRUS"  Link PDF 118pages (http://www.wipo.int/pctdb/images4/PCT-PAGES/2009/092009/09025864/09025864.pdf)

HIV Neutralization ID50 in PBMC Assay: tables on page 39 f. (2F5,13H11,5A9, PPHM Bavituximab, Erbitux (ImClone,BMS,Merck) Anti-CL IS1,4,6 and others

Summary:
What the present studies show is that humans can spontaneously make anti-lipid antibodies and that these antibodies can broadly neutralize HIV in an unprecendented manner.

Summarizing, autoimmune disease patients can make antibodies that bind to virus-infected cells and, presumably, to budding HIV virions by virtue of their reactivity to HIV membranes and host membranes. Certain anti-lipid antibodies from autoimmune disease patients can also react with the Envelope trimer (such as IS6) but not all of the antibodies react also with the trimer (i.e., IS1 and IS4 do not react). Therefore, reactivity with the HIV envelope is not a prerequisite for neutralization in these antibodies.

These studies also demonstrate that it may be possible to safely stimulate the production of IS1 like antibodies in humans using gp41 lipid complexes.
Title: Re: Could this be the holy grail ?
Post by: veritas on July 21, 2009, 06:38:35 am


NICE FIND Matts !!!

That patent seems to be an addition to the patent in the fourth post to this thread!

It's Happening !

Thanks for posting ----- Hopefully,soon we will all see the back-up behind these patents. Timely post.

v
Title: Re: Could this be the holy grail ?
Post by: elf on July 21, 2009, 05:42:09 pm
elf,

Please translate the above post for the benefit of all.

Thanks,

v
Well, basically brazilianman wants to know if this forum has any influence on HIV research, I told him no...The forum is informal, and it's about seeking advice on HIV. I wish we had any influence on HIV research and pharmaceutic companies decisions. :(
Title: Re: Could this be the holy grail ?
Post by: OhioGuyHere26 on July 22, 2009, 06:37:12 pm
Dear Veritas
 
     I have been following all your post for some time now.  I wanted to thank you for providing links, information, and optimism.  I will continue to follow your post and links.  I’m supporting both your effort and hope.

     By the way, is CHAVI on board with testing phases yet?
 
     Also, if you have your own Blog or utube pertaining to these topics, please let me know: I like to join them as well.

Sincerely
Title: Re: Could this be the holy grail ?
Post by: xman on July 22, 2009, 07:13:36 pm
By the way, is CHAVI on board with testing phases yet?

No only a HCV/HIV coinfection trial is ongoing and it is in phase I. We will see the results at the old folks home if we will be still alive and not six feet under for HAART toxicities.

Title: Re: Could this be the holy grail ?
Post by: veritas on July 23, 2009, 09:28:25 am

Ohio,

Thankyou for your kind words.

I believe there is a real opportunity here for a breakthrough since CHAVI was able to muster the first-line hiv researchers in the world to get together to find a vaccine and a cure. When you have the likes of Haynes,Thorpe, Muni, Alam, Moody, Marx, Letvin,Montefiori,Shattock, Yang et al.( See link.}, all working for a common cause, that's gotta be GOOD. It also helps to have the backing of the Gates Foundation ( no mon. /no fun)

https://chavi.org/modules/chavi_invest/index.php?id=38

To answer your question as to CHAVI clinical trials ---- the answer is yes and no. CHAVI is comprised of 10 different cores, all researching different avenues to a vaccine and cure( see: https://chavi.org/modules/chavi_cores/index.php?id=1). As the various cores develop their theories. these theories are tested in vitro and in vivo. So there has been clinical trials in humans (see: https://chavi.org/modules/chavi_trials/index.php?id=1.
What we are all waiting for is  the final product, where all the best theories are brought together in the form of a vaccine or cure to be tested in vivo.... CHAVI will not release any information until they dot every i and cross every t. I anticipate your next question is WHEN! An exact timeline I can't give you, but its closer than we think. Watch for the FOCUS paper in "Nature Medicine" on hiv.

To answer your last question, I chose this forum to develop this thread to reach as many HIV positive people as possible to give them hope and to show that  a cure and a vaccine is being worked on diligently and co-operatively. I knew that I would get some flak using the HOLY GRAIL analogy, but it did get the necessary attention so that quite a few members and guests are reading and following  the thread. I hope it's done some good.

Some believe a vaccine and cure will never be found, I'm not a member of that camp. I know:

IT"S HAPPENING !!!

Stay Healthy,

v




















 



                                                             
Title: Re: Could this be the holy grail ?
Post by: riptide on July 23, 2009, 09:52:31 am
This is some very good stuff but if it was working to combat HIV in addition to HEP C it would be "fast tracked" and we would be hearing more. It would be big news. But so far nothing other than "It could work" pretty much.  I'm keeping my fingers crossed and we'll see.
 I would love to hear more about Gene therapy. It worked in phase I/II trials but no other news. That seems to hold more promiss for treatment of HIV at the moment. What about the guy who found the "Achilles heel" who has a vaccine? Or the guys that "out flank the virus like a general commanding troops" in monkeys? What is happening with those studies? It kills me there isnt more information on this stuff.
Luc Montagnier says likely 4 to 5 years before we'll have vaccines that works but he doesnt comment further. That was a year ago...I'd like to think this guy knows what the hell he is talking about. I just wish there was more information and forward progress. Right now it doesnt seem that way to me.
I hope I am wrong. They have to find a way to get us off the meds.
Title: Re: Could this be the holy grail ?
Post by: veritas on July 23, 2009, 11:32:40 am

riptide,

Funny you asked:

"The present invention relates to viral constructs suitable for use as vaccine vectors for a number of infections including, but not limited to, small pox, West Nile virus,HIV-1,TB, malaria, anthrax and plague.
The vectors can be used, for example, in prime/boost regimins to induce protective and/ or therapeutic immune response to the encoded antigen(s)"


http://www.wipo.int/pctdb/images4/PATENTSCOPE/92/9a/8e/049a8e.pdf

IT'S HAPPENING !!!!!!

v
Title: Re: Could this be the holy grail ?
Post by: riptide on July 23, 2009, 11:47:33 am

 Looks good but its from a few years ago....Is it in any trials to date besides animals? It should have moved forward into some kind of testing by now.
Title: Re: Could this be the holy grail ?
Post by: veritas on July 23, 2009, 01:15:20 pm

riptide,

Please re-read post to Ohio above as to how CHAVI  progresses in clinical trials.

v
Title: Re: Could this be the holy grail ?
Post by: Inchlingblue on July 23, 2009, 01:31:20 pm
  Watch for the FOCUS paper in "Nature Medicine" on hiv.                                                            

Do you know when this is expected? I trust you'll report back when it comes out?  ;)
Title: Re: Could this be the holy grail ?
Post by: veritas on July 23, 2009, 01:39:53 pm

Inch,

It has already been submitted for publication and is presently being reviewed. The exact date for publication -------- ?.

v
Title: Re: Could this be the holy grail ?
Post by: OhioGuyHere26 on July 23, 2009, 05:07:16 pm
     I thought I might share a bit of OTHER information out there on the web and in other laboratories.   Perhaps some of you have already found this and perhaps even followed the stories.  Nonetheless it’s just a bit of other information. 

http://www.newzimbabwe.com/pages/aids36.18565.html

http://www.fox11az.com/news/topstories/stories/NWkmsb20080730_hiv_breakt-hrough.1971ecbd.html
 
Sincerely
Title: Re: Could this be the holy grail ?
Post by: riptide on July 23, 2009, 06:23:18 pm
Ohioguy- Thats a story I was talking about in my previous post. Dr. Paul Sadhir and his crew at UT have developed a couple vaccines but as of now,  7/09  lack the funding needed to go into any type of trials >:(
Title: Re: Could this be the holy grail ?
Post by: xman on July 23, 2009, 07:03:58 pm
Sorry for repeating but what most people here don't consider is that all this great findings are all preliminary study, theories that need scientific evidence which is far away from our actual reality. Clinical trials take years to be completed. The study mentioned above didn't even reach phase I. Researchers and scientists knows that if a trial hasn't at least reached phase II/III, forget it or consider it a theorical approach which needs 5-7 years for reaching the market if ever. It's not to be pessimistic but all this discoveries and studies have been made billions of times over the last 25 years of the epidemic with results that are under the eyes of everyone. There's still nothing to cure HIV or to prevent transmission. As I said in other threads we have to wait at least 10-15 years to be optimistic to see something new in treatment.

Also in my opinion all this testing on animals is a great waste of time since animals react differently to drugs and their viruses are similar but not the same of humans. It is a way to push an industry of laboratory and testing tools and experimentation facilities. Not to mention the ethical aspects involved.
Title: Re: Could this be the holy grail ?
Post by: brazilianman on July 23, 2009, 07:14:18 pm
for all
e-mail   dr.Sudhir Paul:
 <Laura.Nixon@uth.tmc.edu>
<Sudhir.Paul@uth.tmc.edu>
Title: Re: Could this be the holy grail ?
Post by: veritas on July 24, 2009, 05:41:40 am

Ohio,

This thread is for anti-ps and related info. If you want to post about other research please do so , but start another thread. The information becomes confusing to follow if we don't stay on-topic.

Thanks,

v
Title: Re: Could this be the holy grail ?
Post by: veritas on July 24, 2009, 05:52:51 am

xman,

Not only is your thinking faulty and uninformed, it's just plain wrong. I suggest you do more research and not make statements based on your emotions. I suggest you start with the definition of a scid mouse. Please start your own thread.

v
Title: Re: Could this be the holy grail ?
Post by: xman on July 24, 2009, 01:35:12 pm
xman,

Not only is your thinking faulty and uninformed, it's just plain wrong. I suggest you do more research and not make statements based on your emotions. I suggest you start with the definition of a scid mouse. Please start your own thread.

v

unfortunately your researches are very promising but far away from practical applications. we can't benefit from those studies yet and no one nows if we will ever. as i said bavituximab is in a phase 1 clinical trial for hiv and hcv that is still ongoing. we don't know the results. in theory they should be good. as you admitted research is not in our timeline which is exactly what i'm talking about. there's not even one drug or compound ready for use which works differently from actual haart therapies. your entusiasms is well accepted but please don't exceed in optimism and be realistic. the concern for the lack of new drugs for the resistant patients is real and even at ias 2009 the predictions for new treatments and breakthroughs in vaccine developments are seen with scepticism. the actual situation is dramatic concerning new treatments in the pipeline since there's noting in the final testing phases. 
Title: Re: Could this be the holy grail ?
Post by: xman on July 24, 2009, 02:06:56 pm
Luc Montagnier says likely 4 to 5 years before we'll have vaccines that works but he doesnt comment further. That was a year ago...I'd like to think this guy knows what the hell he is talking about.

This kind of announcements were made many times in the past. I remember when Nancy Reagan in 1985 claimed it would be a matter of 2 years to find a vaccine against AIDS. Well now in 2009 we know that Mrs. Reagan was totally wrong. Personally I find those statements unresponsible and insensitive considering all of us hoping desperately in a cure. It is also dangerous because people feel less the need for prevention. Montagnier should spend more time in the labs and stay less in TV studios and conference rooms.
Title: Re: Could this be the holy grail ?
Post by: veritas on July 24, 2009, 02:39:26 pm

xman,

This is the last time I will respond to you. Evidently your search for clinical trials in phase lll  for hiv didn't go far enough. See the following:

http://www.medicalnewstoday.com/articles/152938.php

Please do not post on this thread off topic. This thread is dedicated to anti-ps. Start your own thread.

v
Title: Re: Could this be the holy grail ?
Post by: xman on July 24, 2009, 03:05:19 pm
xman,

This is the last time I will respond to you. Evidently your search for clinical trials in phase lll  for hiv didn't go far enough. See the following:

http://www.medicalnewstoday.com/articles/152938.php

Please do not post on this thread off topic. This thread is dedicated to anti-ps. Start your own thread.

v

I'm not off topic. You're. I was talking about Bavituximab and you mentioned now the Avexa drug which is nothing else than an NRTI addition. We will not defeat the bug with this. Sorry but I don't see the scoop.

This single phase III trial shows the tremendous decrease in the new HAART arsenal.
Title: Re: Could this be the holy grail ?
Post by: brazilianman on July 25, 2009, 08:51:02 am
elf será que voce poderia traduzir para mim, meu inlges e de iniciante ainda. por favor.

vejo que em qualquer forum tem sempre os otimistas e os pessimistas, claro que o veritas é um otimista, não digo isso só por esse embate mas por todos comentarios dele até agora. sim,  o xman é um pessimista e falo isso pelo mesmo motivos que me levaram a pensar que o veritas é um otimista, pelo simples fato da postar mais comentários ruins do que bons. o xman está certo em alguma colocações, penso que existe uma midia entorno dessas supostas novidades, empresas querendo aumentar suas ações e pesquisadores querendo seus 5 mimutos de fama e etc.... mas uma coisa e indicutível NUNCA na história da humanidade uma doença teve tamanha pesquisa em volta dela, falo dos achados que ultimamente tem acontecido, pesquisem a descoberta da penicilina e a maioria vai perceber que além de sorte houve o trabalho, pro caso do hiv o que tem hoje em dia é muito trabalho falto-nos um pouco de sorte, falo da sorte de um cientista descobrir aquilo que fará toda diferença no tratamento. mas concordo com  o veritas que em breve teremos notícias animadoras. se a cura aparecer em 5,10,15 ou 20 anos podem ter ceteza eu vou estar vivo pra usufrir dela.
Title: Re: Could this be the holy grail ?
Post by: veritas on July 25, 2009, 11:00:26 am

brazilianman,

From what little I can translate from your post, you have asked elf to translate  to english. I appreciate that,  because the overwhelming majority of readers speak english. I hope elf will accomodate your request because I am not sure what you are asking or the points you are trying to make. Let's see if this arrangement can work out.

v
Title: Re: Could this be the holy grail ?
Post by: xman on July 26, 2009, 04:47:29 pm
Brazilianman,

Even if I don't speak spanish or portoguese I know very well italian and I understand from your post some missleading considerations about me telling that I'm pessimistic. This is not true! I'm quite realistic indeed. And I'm not alone. Peter Staley, one of the founders of this website agrees too that we are not close to a cure. It can take several years.

Older HIV+ folks know very well the number of disappointments in AIDS research during the last 25 years. As I said before I appreciate the effort of veritas in posting news about the research doing and specifically for bavituximab which seems a good possibility but it needs to be fully proven. Also Bavituximab could be an HAART addition and not a cure.

Without results I don't find it advisable to create hopes for something that is not yet in our reach. For Bavituximab we are only in phase I and Peregrine will not plan further trials before there are encouraging results. If we are lucky it will reach phase III in 2015 and hopefully also for HIV.

Please read the following thread about the chances of something potent coming out soon:
http://forums.poz.com/index.php?topic=26272.0
Title: Re: Could this be the holy grail ?
Post by: veritas on July 26, 2009, 06:22:41 pm

xman,

I'm breaking my own rule not to respond to you because of your mis-representation of facts not only concerning Bavituximab and what Perigrine is doing, but also your conclusions. Perigrine is studying Bavituximab in the setting of Hepc as the main target, whereby, if you had taken the trouble to review their pipeline you could have come to that conclusion.

 Also, if you have read this thread with the appropriate comprehension, you would realize that it is CHAVI doing the research directly for hiv using Perigrine's second generation anti-ps mabs. The Hepc/hiv co-infection trial will only further validate anti-ps, as the cancer trials have already done, which by the way are already in phase ll.

 Since you don't really understand how anti-ps works, let me reiterate that anti-ps does not go after the virus directly, nor does it go after cancer directly. It's target is the inverted ps on the stressed cells. So if anti-ps works in any one of the settings being studied, theoretically it should work for all and that is what has to be proven. By the way, bavituximab has proven better than Avastin (the gold standard for cancer therapy} if you compare both phase l studies for efficacy and safety. The preliminary data from the phase ll cancer trials show Bavituximab superior to Avastin phasell studies. Can you connect the dots?

Now lets look at your timelines. You seem to be all over the place any where from 5 to 20years for new therapies in your various posts. Which is it? The answer is no-one knows exactly and if you re-read this entire thread you will find I have not made any predictions with respect to a timeline.But I'll tell you that should anti-ps get fast-tracked, the wait for anti-ps as a therapeutic for at least one indication will be less than 5 years. That indication could be cancer or viral. Also, you might want to look -up the FDA's animal rule with respect to a multi-faceted therapy and how quickly a new therapy can be approved under that protocol.

Have you ever heard the saying: Past performance doesn't assure future result? That is a frequent quote on Wall Street which can also apply to research. Because a cure,vaccine or kinder gentler therapy hasn't been found doesn't mean it won't be found. As far as I'm concerned your pessimism is legendary and as for me I will not join the ranks of the defeated no matter who they are!

v
Title: Re: Could this be the holy grail ?
Post by: xman on July 26, 2009, 06:57:08 pm
Also, if you have read this thread with the appropriate comprehension, you would realize that it is CHAVI doing the research directly for hiv using Perigrine's second generation anti-ps mabs. The Hepc/hiv co-infection trial will only further validate anti-ps, as the cancer trials have already done, which by the way are already in phase ll.

 Since you don't really understand how anti-ps works, let me reiterate that anti-ps does not go after the virus directly, nor does it go after cancer directly. It's target is the inverted ps on the stressed cells. So if anti-ps works in any one of the settings being studied, theoretically it should work for all and that is what has to be proven.

I was reading the CHAVI trials list page and I wasn't able to find any trials related to anti-ps and HIV. Even on the clinicaltrials.gov page there's only the Peregrine trial listed. If you have a direct link for the trials please post it. Peregrine replied that they are waiting for the results of the currently ongoing phase I trial for HCV/HIV and they will maybe continue with further trials.

veritas, your posts contains many if's. If anti-ps works in any of the settings studied..., if it will be fast tracked..., if, if, if. There's really nothing certain for now. All theories. Let us wait for the first results which will not come out tomorrow. Until then all considerations are pure speculations.

I have another useful link about the treatment developments in the last years and the years to come. Bavituximab is not even mentioned:

http://www.treatmentactiongroup.org/assets/0/16/42/196/198/bfb084dd-e770-4319-8df1-a0efbea7a08d.pdf
Title: Re: Could this be the holy grail ?
Post by: veritas on July 26, 2009, 08:40:54 pm

xman,

You just don't get it. Now I won't waste anymore time with you. Please do not post on this thread anymore. Start your own.

v
Title: Re: Could this be the holy grail ?
Post by: xman on July 27, 2009, 06:23:49 pm
xman,

You just don't get it. Now I won't waste anymore time with you. Please do not post on this thread anymore. Start your own.

v

Yes I probably don't get it but you are putting too much hope in something that is not even in phase III trials and needs to answer a lot of questions yet.
Title: Re: Could this be the holy grail ?
Post by: veritas on July 30, 2009, 10:01:14 am


Dr. Thorpe to speak at IBC & GRC Conf’s

Dec6-10 2009: IBC’s 20th Annual Intl. Conf – “Antibody Engineering & Immunotherapeutics for the 21st Century”, SanDiego
Session VIII: Engineering Antibodies to Improve Cancer Therapy
Chair: Dr. Louis Weiner, Dir., Lombarbi Comprehensive C.C., Georgetown Univ. MC
Dec10 3:45pm: Philip E. Thorpe (PhD, UTSW-MC): “Targeting Exposed PS on Cancer Blood Vessels & Viruses”
Abstract: Phosphatidyserine (PS) is confined to the inner leaflet of the plasma membrane in resting mammalian cells. It becomes exposed on tumor blood vessels and on virus-infected cells in response to cell activation and oxidizing stresses. We had developed therapeutic monoclonal antibodies that cause innate immune cells to target & destroy PS-expressing tumor blood vessels and virus-infected cells. Bavituximab, our leading anti-PS antibody, is showing good efficacy in clinical trials.
http://www.ibclifesciences.com/upload/wysiwyg/drug_discovery_series/D9172/D9172agenda.pdf

IT"S HAPPENING !!!


v
Title: Re: Could this be the holy grail ?
Post by: veritas on July 30, 2009, 10:39:31 am

Matts,

You asked what is happening with DITRA with Bavituximab in an earlier post:

DTRA wants a broad spectrum anti-viral that will work against multiple viral diseases, even if they have not been seen before or identified. They think they may have it in bavituximab, and in order to test  the mAb they have contracted Peregrine for up to $44.4 million. This constitutes one of their largest bio-research contracts.

If they do confirm that this mAb has this capability, they will apply for emergency approval, which FDA will grant, and Peregrine Pharmaceuticals will have an approved fully human version of bavituximab ready to market commercially for the treatment of multiple viruses. What would be the further possibilities for an approved fully human bavi mAb in other indications at that point?

IT'S HAPPENING !!!

v

ps: you asked why we haven't heard? How about this:

http://esignal.brand.edgar-online.com/EFX_dll/EDGARpro.dll?FetchFilingPDF1?SessionID=GdAFWJ3XXzpGD7h&ID=6704132
Title: Re: Could this be the holy grail ?
Post by: veritas on July 30, 2009, 10:59:47 am

Another study --- it's the anionic lipids again:

http://www.ncbi.nlm.nih.gov/pubmed/19400584?ordinalpos=1&itool=Email.EmailReport.Pubmed_ReportSelector.Pubmed_RVDocSum

"We concluded that TAT peptides are not incorporated into but rather floating on lipid bilayers, but they immerged deeper into the headgroup domain of anionic lipids. "

v
Title: Re: Could this be the holy grail ?
Post by: brazilianman on July 30, 2009, 12:05:00 pm
veritas. you could translate.

 what is tat? which is lipid bilayers? how it works? and how it will help us?
Title: Re: Could this be the holy grail ?
Post by: veritas on July 30, 2009, 01:18:20 pm

braziliaman,

tat--  http://www.mcld.co.uk/hiv/?q=tat

lipid bilayers -----  http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mboc4.section.1864
The most abundant membrane lipids is the phospholipids.

How it works? -----  see above link.

How it will help us? ---- Anti -ps therapy attaches to the exposed ps in infected cells and the virus to summon the immune system to kill it.

v
Title: Re: Could this be the holy grail ?
Post by: xman on July 30, 2009, 02:11:08 pm
If they do confirm that this mAb has this capability, they will apply for emergency approval, which FDA will grant, and Peregrine Pharmaceuticals will have an approved fully human version of bavituximab ready to market commercially for the treatment of multiple viruses.

believe me, i really, really hope you're right. but please explain why you're so optimistic that it works with hiv. are there any clinical tests that confirms this? my concern is that they will only approve for cancer treatment putting hiv behind. what demonstrates bavituximab activity on the reservoirs? i mean are we sure latent infected cells expose ps?
Title: Re: Could this be the holy grail ?
Post by: veritas on July 31, 2009, 05:16:27 pm

What else can anti-ps do?
How about not only targeting but also imaging tumor vasculature.


Patent app #20090191121, 12/371458, filed 2-13-09
Thorpe; Philip E. ; et al. July 30, 2009
“Targeting and Imaging Tumor Vasculature Using Conjugates That Bind to Aminophospholipids”
ABSTRACT
Disclosed is the surprising discovery that aminophospholipids, such as phosphatidyserine and phosphatidylethanolamine, are specific, accessible and stable markers of the luminal surface of tumor blood vessels. The present invention thus provides aminophospholipid-targeted diagnostic and therapeutic constructs for use in tumor intervention. Antibody-therapeutic agent conjugates and constructs that bind to aminophospholipids are particularly provided, as are methods of specifically delivering therapeutic agents, including toxins and coagulants, to the stably-expressed aminophospholipids of tumor blood vessels, thereby inducing thrombosis, necrosis and tumor regression.
INVENTORS:
Thorpe; Philip E.; (Dallas) ; Ran; Sophia; (Dallas) ; Brekken; Rolf A.; (Seattle)
Correspondence: PEREGRINE PHARMACEUTICALS, INC., 5353 W. ALABAMA, HOUSTON TX
Assignee: The University of Texas System
[0002] The U.S. Gov’t owns rights in the present invention pursuant to grant numbers 1RO1CA74951-01 & 5RO1CA54168-05 from the NIH.
. . .
[0054] One of the benefits of the present invention is that aminophospholipids, particularly phosphatidylserine and phosphatidylethanolamine, are generally expressed or available throughout the tumor vessels. Aminophospholipid expression on established, intratumoral blood vessels is advantageous as targeting and destroying such vessels will rapidly lead to anti-tumor effects. However, so long as the administered therapeutic agent-targeting agent constructs bind to at least a portion of the blood transporting vessels, significant anti-tumor effects will ensue. This will not be problematical as aminophospholipids, such as phosphatidylserine and phosphatidylethanolamine, are expressed on the large, central vessels, and also on veins, venules, arteries, arterioles and blood transporting capillaries in all regions of the tumor.
. . .
[0174] The entire range of therapeutic agent-targeting agent construct, as described above, may be employed in the kits, medicaments and/or cocktails, with annexin conjugates and constructs; anti-PS, anti-PE, human, humanized and monoclonal antibody conjugates and constructs; ricin conjugates; and Tissue Factor conjugates and constructs being preferred. The anti-cancer agents are also those as described above, including chemotherapeutic agents, radiotherapeutic agents, anti-angiogenic agents, apoptopic agents, immunotoxins and coaguligands. Agents formulated for intravenous administration will often be preferred.
. . .
v
Title: Re: Could this be the holy grail ?
Post by: veritas on July 31, 2009, 05:22:21 pm

I also see that Drs. Haynes and Alam et al. are not sitting on their hands:

http://www.ncbi.nlm.nih.gov/pubmed/19640992?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

It's those membranes and lipids again and of course MABS !

It's Happening !!

v
Title: Re: Could this be the holy grail ?
Post by: brazilianman on August 04, 2009, 04:59:52 pm
hello veritas

Hi found this link on bavituximab. so please not too much. which is 0.5 log10 reduction? in porcetagem is about?
 
www.drugs.com/.../positive-results-peregrine-pharmaceuticals-bavituximab-phase-l-hcv-trial-presented-aasld-meeting-2568.ht... -
Title: Re: Could this be the holy grail ?
Post by: xman on August 04, 2009, 05:29:39 pm
brazilianman,

your link doesn't work

i guess that is old news. there are no updates on the peregrine homepage.
Title: Re: Could this be the holy grail ?
Post by: brazilianman on August 04, 2009, 05:36:35 pm
sorry
http://www.drugs.com/clinical_trials/positive-results-peregrine-pharmaceuticals-bavituximab-phase-l-hcv-trial-presented-aasld-meeting-2568.html
Title: Re: Could this be the holy grail ?
Post by: brazilianman on August 04, 2009, 06:21:36 pm
BAVITUXIMAB HCV

http://www.natap.org/2007/AASLD/AASLD_74.htm
Title: Re: Could this be the holy grail ?
Post by: veritas on August 05, 2009, 08:52:33 am
braziliaman,

That is indeed a study (phase 1 ) from 2007. It was done mainly as a safety study and they found Bavituximab safe at all dose levels. The antibody showed anti-viral activity. Please understand that the 3g4 antibody used is the first anti-ps antibody in clinical trials (HOWEVER NOT THE STRONGEST). The antibodies being used by CHAVI are much stronger for their vaccine development. This trial proved not only that Bavituximab was safe but also proved the concept for anti-ps therapy as an anti-viral agent.
Thankyou for posting !

v
ps:"The 3mg/kg cohort had the largest number of patients showing antiviral activity, as 5 of 6 subjects achieved >0.5 log decline in HCV RNA."
They did not report the actual viral decline for each patient.
Title: Re: Could this be the holy grail ?
Post by: brazilianman on August 05, 2009, 01:21:14 pm
veritas
very good bavituximab monotherapy. 2 aplication reduction > 75% RNA VHC.
Title: Re: Could this be the holy grail ?
Post by: xman on August 05, 2009, 08:30:45 pm
The antibodies being used by CHAVI are much stronger for their vaccine development.

how long are these in development and when will the human trials begin? i can't understand why we are still waiting for them.
Title: Re: Could this be the holy grail ?
Post by: veritas on August 06, 2009, 05:47:45 am

Article: Could one drug kill all germs?

newscientist

"... Perhaps the most promising broad-spectrum antiviral is being developed by Philip Thorpe, a pharmacologist at the University of Texas Southwestern Medical Center in Dallas. Like Goldblatt, Thorpe has discovered a "footprint" of viral infections."

"... If these drugs live up to their promise, it will be a breakthrough on a par with the development of penicillin"

http://www.newscientist.com/article/mg20327200.100-could-one-drug-kill-all-germs.html?full=true

It's Happening !

v
Title: Re: Could this be the holy grail ?
Post by: brazilianman on August 06, 2009, 06:07:51 pm
veritas

I think anti-ps is used with HAART.
how long HIV remained in the cell? same latent that day has a cell to die.
Title: Re: Could this be the holy grail ?
Post by: veritas on August 07, 2009, 04:53:41 am

braziliaman,

You said " I think anti-ps is used with HAART".  How did you come to that conclusion?

I don't understand your second question. What do you mean " how long HIV remained in the cell? same latent that day has a cell to die." ?

v
Title: Re: Could this be the holy grail ?
Post by: brazilianman on August 07, 2009, 09:22:14 am
veritas
it is not conclusion is only my thought
anti-ps could be used with haart to increase the results.
the other questions are on the time of life of hiv in the cell.
all cell with hiv dies?
Title: Re: Could this be the holy grail ?
Post by: veritas on August 07, 2009, 09:43:08 am

braziliaman,

Hopefully, it won't be necessary to take HAART. The free flowing virus carries exposed -ps on the viron so if the immune response is strong enough you shouldn't need HAART. I understand your thinking though ( get rid of the free-flowing virus as quickly as possible). Let's hope it's not necessary.

As for your second question --- theoreticaly, all cells infected with HIV (including latent cells) expose ps and as such are a target for anti-ps. If the antibodies produce a strong enough immune response, they will go after both freeflowing virus and infected cells at the same time.

v
Title: Re: Could this be the holy grail ?
Post by: brazilianman on August 07, 2009, 09:58:02 am
veritas

this is wonderful

I love anti-ps
Title: Re: Could this be the holy grail ?
Post by: veritas on August 07, 2009, 10:08:52 am

braziliaman,

I love it also, but we must wait for research results. All research thus far has been positive. If anyone can find a negative peer review please post. I have not found any.

v
Title: Re: Could this be the holy grail ?
Post by: brazilianman on August 08, 2009, 10:36:39 am
veritas
to eliminate HIV from the brain?

''He said it is not known whether Bavituximab crosses the BBB , but that he would not be surprised if it does not.''

http://www.bmedreport.com/archives/4486 # more-4486
 
Title: Re: Could this be the holy grail ?
Post by: brazilianman on August 08, 2009, 11:17:39 am
nature journal

inside hiv1

http://www.nature.com/nature/journal/v460/n7256/
Title: Re: Could this be the holy grail ?
Post by: Inchlingblue on August 08, 2009, 12:41:35 pm

http://www.bmedreport.com/archives/4486 # more-4486
 


from link above:

Dr. Thorpe stated that the active (i.e., viral replication) phase always appears to triggers exposure of phosphatidylserine, but that it is currently unknown whether cells in which the virus has become dormant, or ‘latent’, will continue to have exposed phosphatidylserine.

So I guess it's not known if bavituximab can reach HIV reservoirs at this point?

nature journal

inside hiv1

http://www.nature.com/nature/journal/v460/n7256/

This is being discussed in another thread:

http://forums.poz.com/index.php?topic=28339.0
Title: Re: Could this be the holy grail ?
Post by: elf on August 08, 2009, 12:58:29 pm
This kind of announcements were made many times in the past. I remember when Nancy Reagan in 1985 claimed it would be a matter of 2 years to find a vaccine against AIDS. Well now in 2009 we know that Mrs. Reagan was totally wrong. Personally I find those statements unresponsible and insensitive considering all of us hoping desperately in a cure. It is also dangerous because people feel less the need for prevention. Montagnier should spend more time in the labs and stay less in TV studios and conference rooms.
Unfortunately, for pharmaceutic companies, HIV is just a tropical disease killing millions of people in poor countries, just like malaria, schistosomiasis, leishmaniasis, trypanosomiasis...they're not interested in finding a vaccine, their excuse is always the same: it's too difficult... (it's just like a mother telling her child: you should study; but the child says: it's to difficult, and he doesn't study :( )
Title: Re: Could this be the holy grail ?
Post by: brazilianman on August 08, 2009, 01:05:20 pm
verita

http://www.nature.com/nature/supplements/collections/hivaids/
Title: Re: Could this be the holy grail ?
Post by: veritas on August 09, 2009, 05:42:57 am

braziliaman,

Dr. Hayne's paper is not included in this focus paper. I know his paper has been submitted for publication, so the review process for his submittal has not been completed----- we wait somemore.

Inch,

We discussed Thorpe's interview earliar in this thread concerning the BBB and latent cells. Further along in the interview Thorpe says:


"Also, he said that it is not known whether cells infected with viruses like these which can become latent will continue to have exposed phosphatidylserine. He went on to state that this may not matter because the current thought is that you might be able to deplete the pool of virus during the active phase of infection and if the latent pool of virus can not be replenished then it will die out. "

The final answer is they don't know yet ,however it does not matter.


v
Title: Re: Could this be the holy grail ?
Post by: veritas on August 09, 2009, 10:46:59 am

Exposed ps on infected cells:

http://www.newscientist.com/data/images/archive/2720/27200101.jpg


v
Title: Re: Could this be the holy grail ?
Post by: Inchlingblue on August 09, 2009, 12:29:46 pm

We discussed Thorpe's interview earliar in this thread concerning the BBB and latent cells. Further along in the interview Thorpe says:


"Also, he said that it is not known whether cells infected with viruses like these which can become latent will continue to have exposed phosphatidylserine. He went on to state that this may not matter because the current thought is that you might be able to deplete the pool of virus during the active phase of infection and if the latent pool of virus can not be replenished then it will die out. "

The final answer is they don't know yet ,however it does not matter.


v

I'm not sure why you say it wouldn't matter if ps is exposed in latent cells when it comes to HIV? The quote you cite seems like he is talking about herpes and EBV, since it comes right after they are mentioned and since the reasons he gives for it not mattering don't seem to make sense if one is talking about HIV (some of HIV's latent pool may die out but it would take decades plus it's been shown in very recent research that there is still some Tcell division in the reservoirs). As far as depleting the pool "during active phase of infection," that also doesn't make sense with HIV. I don't think he was referring to HIV when he said those things.

 Dr. Thorpe further responded that Bavituximab has not been studied with genital or oral herpes or EBV. Also, he said that it is not known whether cells infected with viruses like these which can become latent will continue to have exposed phosphatidylserine. He went on to state that this may not matter because the current thought is that you might be able to deplete the pool of virus during the active phase of infection and if the latent pool of virus can not be replenished then it will die out

I'm not knocking anti-ps. Even if it did not reach reservoirs, it seems we'd then be looking at either taking it for life or having long-term infusions of it, but at least mutations or toxicities would not be an issue.
Title: Re: Could this be the holy grail ?
Post by: xman on August 09, 2009, 01:06:42 pm
it seems we'd then be looking at either taking it for life or having long-term infusions of it, but at least mutations or toxicities would not be an issue.

the holy grail!
Title: Re: Could this be the holy grail ?
Post by: brazilianman on August 09, 2009, 02:03:28 pm
veritas

 news from nature

 focus hiv research

http://www.nature.com/nm/index.html
Title: Re: Could this be the holy grail ?
Post by: Inchlingblue on August 09, 2009, 02:29:06 pm

I'm not knocking anti-ps. Even if it did not reach reservoirs, it seems we'd then be looking at either taking it for life or having long-term infusions of it, but at least mutations or toxicities would not be an issue.

To correct what I said: I didn't mean to say "taking it for life," since anti-ps is an antibody immune response. It may be that one vaccine can induce such a response for life, assuming the person has a strong enough immune system.

Maybe more than one vaccine would be necessary or maybe the antibodies can be directly infused, these are all unanswered questions as far as I know.

The point is, this is very promising research.

Thanks again, Veritas, for updating this excellent thread.

 
Title: Re: Could this be the holy grail ?
Post by: brazilianman on August 09, 2009, 03:53:10 pm
they do not say to nothing of the Dr. Haynes in the focus hiv and nor in the supplemen.
nothing of anti-ps .
Title: Re: Could this be the holy grail ?
Post by: veritas on August 10, 2009, 05:53:26 am

Inch,

Glad to see your second post ! The adaptive immune response as seen in preclinicals should take care of redosing problem if the immune response is strong enough. This means (obviously) that if ps is not exposed on resting cells (and we don't know this yet!) your immune system should remember how to tackle the virus without further dosing. A lot of data still hasn't been released.

No matter what enveloped virus your talking about the MOA is the same.

braziliaman,

In a previous post I explained that Dr. Haynes paper on anti -ps has not completed the review process yet that is why you didn't see it in the focus supplement. You must remember that anti-ps is a new paradigm in the fight against HIV so reviews will be more vigorous. I was hoping the review process would be completed before the focus paper came out. ---- so we wait.

v

v
Title: Re: Could this be the holy grail ?
Post by: veritas on August 10, 2009, 04:14:27 pm

Somemore B Haynes, but not the one were waiting for:







J. Virol. JVI Table of Contents for 1 September 2009; Vol. 83, No. 17

T-Cell Vaccine Strategies for Human Immunodeficiency Virus, the Virus with
a Thousand Faces
Bette T. Korber, Norman L. Letvin, and Barton F. Haynes
J. Virol. 2009;83 8300-8314
http://jvi.asm.org/cgi/content/full/83/17/8300?etoc

Antibody Specificities Associated with Neutralization Breadth in Plasma
from Human Immunodeficiency Virus Type 1 Subtype C-Infected Blood Donors
Elin S. Gray, Natasha Taylor, Diane Wycuff, Penny L. Moore, Georgia D.
Tomaras, Constantinos Kurt Wibmer, Adrian Puren, Allan DeCamp, Peter
B. Gilbert, Blake Wood, David C. Montefiori, James M. Binley, George
M. Shaw, Barton F. Haynes, John R. Mascola, and Lynn Morris
J. Virol. 2009;83 8925-8937
http://jvi.asm.org/cgi/content/abstract/83/17/8925?etoc

v
Title: Re: Could this be the holy grail ?
Post by: xman on August 10, 2009, 04:40:16 pm
the first link is only for registered members. could you post a summary of it?
Title: Re: Could this be the holy grail ?
Post by: brazilianman on August 12, 2009, 09:13:47 am
veritas

I was analyzing the case of American cured in Germany. whether the first reduction in viral load with HAART. and was the second transplant with the CCR5 mutation. new cells were created with this mutation. zinc finger can function. with therapy with other anti-ps. I think the cure may be close. just one way to put it into operation.
Title: Re: Could this be the holy grail ?
Post by: veritas on August 19, 2009, 04:56:31 am


It's those lipids and mabs again - this time with cholesterol:

http://www.jlr.org/cgi/rapidpdf/jlr.M000372v1.pdf

It's happening!

v
Title: Re: Could this be the holy grail ?
Post by: veritas on August 19, 2009, 05:11:26 am

Dr. Philip Thorpe ( father of anti-ps) gets another grant :

http://crisp.cit.nih.gov/crisp/CRISP_LIB.getdoc?textkey=7452671&p_grant_num=1U01AI077844-01&p_query=&ticket=102749882&p_audit_session_id=489316668&p_keywords=

This time for Broad spectrum  treatment for Hemmorrhagic arenaviruses.

Growing interest in anti-ps for various indications ---- do you think it's happening ? You betcha!

v
Title: Re: Could this be the holy grail ?
Post by: veritas on August 20, 2009, 04:08:30 am

The following is why a preventative vaccine is so difficult to achieve:

http://www.ncbi.nlm.nih.gov/pubmed/19625640?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

Let's hope a therapeutic is not as difficult.

v
Title: Re: Could this be the holy grail ?
Post by: Inchlingblue on August 20, 2009, 11:23:16 am
That's why for me one of the most exciting and important recent discoveries, which was discussed in one of the threads, is the one that entails directly injecting into muscle tissue (by way of an adenovirus vector) DNA that produces antibodies (immunoadhesins), essentially bypassing the immune system altogether.

The viruses load the genes into the nuclei of muscle cells, which produce and churn out the immunoadhesins, potentially indefinitely. "Instead of expecting the person's own immune system to do the job, we're giving them their own supply of 'off-the-peg' antibodies," Johnson says.

LINK:

http://forums.poz.com/index.php?topic=27194.0
Title: Re: Could this be the holy grail ?
Post by: veritas on August 22, 2009, 05:19:21 am

Exposed ps on tumors:

http://www.benthamdirect.org/pages/content.php?CPD/2009/00000015/00000023/0008B.SGM

v
Title: Re: Could this be the holy grail ?
Post by: xman on August 22, 2009, 01:05:04 pm
Great. Any news reguarding HIV?

Title: Re: Could this be the holy grail ?
Post by: veritas on August 23, 2009, 02:33:11 pm


"Regulation of Broadly Neutralizing Antibody Responses: The Initial B Cell Repertoire To HIV-1 Envelope
Barton Haynes, Duke University Medical Center, USA "

http://www.hivvaccineenterprise.org/conference/2009/scientific_program.aspx

v
Title: Re: Could this be the holy grail ?
Post by: veritas on August 25, 2009, 05:01:40 am

Research in progress:

http://www3.niaid.nih.gov/news/newsreleases/2009/HVTN505.htm

"The Ad5 vaccine in this study encodes for HIV proteins found both inside the virus and on its outer envelope."

v
Title: Re: Could this be the holy grail ?
Post by: veritas on August 26, 2009, 09:34:18 am


The beat goes on, the hope never dies ( another grant for anti-ps ):

http://www.earthtimes.org/articles/show/niaid-awards-new-grant-to,937690.shtml

v
Title: Re: Could this be the holy grail ?
Post by: brazilianman on August 27, 2009, 10:07:06 am
veritas

 ???  if the positive test result HIV / hepatitis C bavituximab. should have it released for consumption in 3 years. I am dying to see the results. and decreased viral load. the AE after repeated infusions. as our immune system will work. these questions must be answered. ???
Title: Re: Could this be the holy grail ?
Post by: sam66 on August 29, 2009, 08:17:20 am
hi,  this thread is full of technical stuff,

 could someone please explain to me in laymans terms, what this research could mean to +ve people.

   ta
Title: Re: Could this be the holy grail ?
Post by: veritas on August 29, 2009, 09:05:37 am

braziliaman,

Please remember that the antibody being used in the co-infection trial is the first anti-ps antibody found and the antibodies being used by CHAVI are a lot more potent. My statement does not mean to infer that the antibody being used in the co-infection trial will not work against hiv but rather it might not be potent enough to eliminate the virus. However, I'm with you--- if it can control the virus without the necessity of HAART I'm all for it. The wait for the cure would be a lot easier.

sam66,
In laymens terms, anti-ps is a new way to fight the virus by attaching  to a portion of the virus that the virus can't mutate against, thus potentially having the ability to control the virus without HAART meds. It is also being studied as a cure and a vaccine.

v
Title: Re: Could this be the holy grail ?
Post by: sam66 on August 29, 2009, 10:02:10 am
thanks  veritas,

                 now i know whats going on,
Title: Re: Could this be the holy grail ?
Post by: veritas on August 31, 2009, 05:15:36 am

Transformational Medical Technologies Initiative (TMTI) for bio-defense threat.

Bavituximab along with a handfull  of other technologies being studied for Ebola and Junin fever as a broard spectrum anti-viral defense. Notice slide 11:

http://trueresearch.org/aerobiology/abstract/session%207/Wargo%20TMTI%20Overview%2016July09.ppt



IT'S HAPPENING!

v
Title: Re: Could this be the holy grail ?
Post by: veritas on August 31, 2009, 09:30:47 am


Dr. Bruce Cabner, noted oncologist, lends expertise to the clinical development of Bavituximab:

http://www.reuters.com/article/pressRelease/idUS111100+31-Aug-2009+PRN20090831

Does he have any experience with HIV and  OI's? --- Read some history!

http://history.nih.gov/NIHInOwnWords/docs/chabner1_01.html

These words from "The Lion of the Senate" sums up my belief in anti-ps and HIV research:

"The work goes on, the cause endures, the hope still lives, and the dream will never die!"

It's Happening!

v
Title: Re: Could this be the holy grail ?
Post by: xman on August 31, 2009, 01:31:03 pm
OK excellent. I'm still a bit concerned about the fact that HIV is not much mentioned in any article and report. It seems still a secondary endpoint. In the top of agenda is cancer and extremely dangerous viruses like Ebola. If they fast track research on those treatments HIV could still stay behind. It's an impression from me and I'm probably wrong. Maybe veritas can explain that better.

I took also another look to the ongoing phase I trial of bavituximab from peregrine and they are still recruiting partecipants. I guess we will not see results in September as stated in the trial.
Title: Re: Could this be the holy grail ?
Post by: steppenwolf on September 01, 2009, 01:42:20 pm
Peregrine Pharmaceuticals to Present at the Rodman & Renshaw 11th Annual Healthcare Conference

- Presentation to Be Webcast Live On Company's Website -

TUSTIN, Calif., Sept 01, 2009 /PRNewswire-FirstCall via COMTEX News Network/ -- Peregrine Pharmaceuticals, Inc. (Nasdaq: PPHM) today announced that senior management will present at the Rodman & Renshaw 11th Annual Healthcare Conference on Thursday, September 10, 2009 at 10:25 am EDT. The conference will be held at the New York Palace Hotel in New York City.

A live webcast of the company's presentation will be available at the Investors section of Peregrine's website at www.peregrineinc.com. A replay will be available on the Peregrine website and archived for 90 days.

For more information about this conference, please visit: http://www.rodmanandrenshaw.com/conferences?id=30
Title: Re: Could this be the holy grail ?
Post by: Carlos3000 on September 03, 2009, 06:12:29 pm
hi, , some news online

http://www.positivelypositive.ca/hiv-aids-news/IAVI-Two_New_Antibodies_Found_to_Cripple_HIV.html

http://www.newscientist.com/article/dn17733-discovery-of-hivs-weak-spot-boosts-vaccine-quest.html
Title: Re: Could this be the holy grail ?
Post by: veritas on September 03, 2009, 07:18:17 pm
Carlos,

Great find!  

What stood out for me upon reading your links was the following:

"One, codenamed PG9, neutralised 127 of 162 HIV strains and the other, codenamed PG16, neutralised 119."

This shows what collaboration can do. The greater the number of antibodies that can be incorporated into a vaccine ,the stronger the immune response. Since they obtained these antibodies from someone who is controlling the virus, this bodes well for it's therapeutic value.

Thanks for posting!

"The work goes on."



v
Title: Re: Could this be the holy grail ?
Post by: veritas on September 04, 2009, 05:25:50 am

Carlos,

Here is a an image of the antibodies and the virus:


http://www.scripps.edu/news/press/images/20090831_IAVI/HIV-1_trimer.jpg


Caption: Modeling the PG9 and PG16 epitopes onto the HIV-1 trimer. The above model is adapted from a recent cryo-electron tomographic structure of the HIV-1 trimer. The crystal structure of the gp120 core (orange) has been fitted into the density map. The V1/V2 and V3 loops, which are not resolved in the crystal structure, are represented as green and yellow ovals, respectively. The approximate locations of gp41 and the viral membrane (not resolved in the structure) are shown in blue. The red structure located above the trimer is a human IgG molecule representative of PG9 and PG16. The PG9 and PG16 epitopes are believed to involve residues in the V1/V2 and V3 loops of gp120.

v

Title: Re: Could this be the holy grail ?
Post by: veritas on September 04, 2009, 05:45:30 am

Steven King, president of pphm, answers question pertaining to anti-viral program on yesterday's conference call:

My question in regard to the company is a very exciting antiviral program and the scarcity of public information about them; everyone understands that these programs have been paid for with other people’s money like Duke and NIH, and they should be the first to get the spotlight, but after the Nature Medicine article was published, will you be able to talk more freely about things, non-DPRA, things like aerosol delivery, HIV microbicides, possible swine flu applications, etc., or will the public secrecy have to remain over those antiviral programs?

Steven W. King

Yes, it’s a good question, and certainly our goal is to see a number of publications, presentation, and such coming from this research to really just to let the public know how the programs are proceeding and what the results are looking at as they move forward, and also that things shine a light on what our future plans are for the program. So, I think we’ll have opportunities actually to not just talk about it or publish the work we’re doing with our collaborators like Duke and the other institutions involved in researching our antiviral applications of our PS technology, but also even some opportunities present data from the DPRA contract work and shine some light on how those studies are proceeding, and I believe that all of our collaborators are equally interested in seeing that information get out there in really the right formats and in the right settings. So, all those preparations are in work and I think you’ll see more coming out of the programs from a public standpoint over the coming months, and certainly we’re excited to get that information out there because we’re very happy with the way all of these studies are progressing and what we’re seeing in the pre-clinical study.

v
Title: Re: Could this be the holy grail ?
Post by: veritas on September 04, 2009, 08:26:02 am

Another follow-up to PG9 and PG16 antibodies:

http://www.bloomberg.com/apps/news?pid=20601124&sid=akGVjigUJynU

The sentence in the above link that I found intriguing was the following:


"The antibodies themselves can’t simply be put in a vaccine to immunize people against HIV, said Wayne Koff, senior vice president of research and development at the Vaccine Initiative in New York. While such an effort could have a short-term benefit, a successful vaccine will teach people’s immune systems to produce their own powerful antibodies"

I wonder what type of delivery system they will need?  ( anti-ps anyone!).

It's Happening!

v
Title: Re: Could this be the holy grail ?
Post by: veritas on September 04, 2009, 08:47:13 am
In the above link, click on GRAPHIC at the top of the story. The graphic shows how difficult it would be for those antibodies to find the appropriate target. Also in that graphic, see how the virus shields itself from the immune system. For anyone following this thread, they know that those immune shielding appendicies are flipped ps. Bavi shines the light, allowing the immune system to do it's job.

"The work goes on"!

v
Title: Re: Could this be the holy grail ?
Post by: Inchlingblue on September 04, 2009, 11:44:44 am
The sentence in the above link that I found intriguing was the following:


"The antibodies themselves can’t simply be put in a vaccine to immunize people against HIV, said Wayne Koff, senior vice president of research and development at the Vaccine Initiative in New York. While such an effort could have a short-term benefit, a successful vaccine will teach people’s immune systems to produce their own powerful antibodies"
 

Another way would be to directly inject into muscle the genes that are responsible for the antibodies, producing a potentially endless supply and bypassing the immune system altogether. One of the articles mentioned that they isolated these genes.

For those who might be confused: PG9 and PG16 are not anti-ps antibodies.

I started a new thread for this in order to avoid confusion.
Title: Re: Could this be the holy grail ?
Post by: veritas on September 04, 2009, 02:20:47 pm


Inch,

Your absolutely correct that the PG9 and PG16 antibodies are not anti-ps antibodies. Neither are 4E10,2F5 or 2g12 antibodies. These are the killer antibodies to the virus. Anti-ps antibodies (3g4, IS4,etc.) are the anti-ps antibodies that attach to the flipped ps on the virus and infected cells. Anti-ps antibodies do not kill the virus. They eliminate the viral shield that the virus uses to evade the immune system They "shine the light"   on the virus so the immune system can do it's job. Think of the PG9 and PG16 as missiles that need to be guided to their target. Anti-ps is the guidance system allowing them to do their job. Yes, these super killer antibodies were found in an elite controller, that was keeping the virus at bey (in effect a functional cure), however that controller was and is HIV+.

Now if you bring up the graphic posted in the Bloomberg link above, you can see the gp120 target that these antibodies go after. That target is partially hidden thus some of the virus will always escape. That's why this elite controller was not able to eradicate the virus from his system. The antibodies find enough of them to prevent progression to AIDS in the blood but they cannot reach the latent cells since their target is on the virus itself. Thiese antibodies are very powerful and do their job efficiently, however, eradication can not occur without elimination of all infected cells. This find just might be the necessary immune response to that end along with anti-ps antibodies to guide them.

This find makes me more hopeful than ever that their will be a cure and a vaccine for this disease in our lifetime.

v

ps: By the way, I'd certainly take a functional cure but I believe that better things are afoot. It's Happening!
Title: Re: Could this be the holy grail ?
Post by: veritas on September 04, 2009, 03:36:25 pm

Hot off the press --- researchers believe they have found a way  to produce broadly neutralizing anti-bodies:

http://www.sciencedaily.com/releases/2009/09/090901143319.htm

"It has been believed that it might be difficult to induce such antibodies experimentally, and historically, this has been considered a potential roadblock to creation of an effective HIV vaccine. This study demonstrates that such antibodies might be induced with immuno-stimulating liposomes"

The study:

http://journals.lww.com/aidsonline/Abstract/publishahead/Neutralizing_antibodies_induced_by_liposomal_HIV_1.99750.aspx

v
Title: Re: Could this be the holy grail ?
Post by: veritas on September 04, 2009, 03:54:38 pm


The previous post showed how using liposomes  can allow the immune system to develop anti-HIV antibodies. But what is a liposome?:

http://encyclopedia2.thefreedictionary.com/Liposomes

Liposomes have numerous uses as biochemical and biophysical tools: (1) as vehicles for the delivery of both water- and of oil-soluble materials to the cell; (2) as immunological adjuvants; (3) as substrates for the study of membrane properties such as rotational or translational diffusion in the plane of the membrane; and (4) as intermediates in the construction of bilayers large enough for the study of electrical properties of membranes

v
Title: Re: Could this be the holy grail ?
Post by: Inchlingblue on September 04, 2009, 05:46:31 pm
v, your thread is getting confusing (to me at least)...isn't this what was being discussed in a recent thread entitled "Researchers Induce HIV-neutralizing Antibodies against envelope protein+ lipids"?

http://forums.poz.com/index.php?topic=28778.0 (http://forums.poz.com/index.php?topic=28778.0)
Title: Re: Could this be the holy grail ?
Post by: veritas on September 05, 2009, 04:40:41 am

The relevant paragraph in the study in the following link:

http://journals.lww.com/aidsonline/Abstract/publishahead/Neutralizing_antibodies_induced_by_liposomal_HIV_1.99750.aspx

is as follows:

The discovery of the novel lipid-binding properties of 2F5 and 4E10 has generated interest in the possibility that the binding of the antibodies to lipids themselves might participate as a part of the neutralizing mechanism of certain types of antibodies [17,22]. By utilizing liposomal methodology for inducing antibodies to lipids [23,24], a murine antiphosphatidylinositol-4-phosphate (anti-PIP) mAb (WR304) was produced that exhibited neutraliz­ation of infection by two primary HIV-1 isolates in a peripheral blood mononuclear cell (PBMC) assay but lacked any activity in the corresponding pseudovirus assay utilizing TZM-bl cells [25]. These observations were subsequently confirmed with several human IgG mAbs [PGN632, P1, IS4-, and CL1] that exhibited beta2­glycoprotein I-independent binding to pure phospholi­pids and that also neutralized in the PBMC assay but not in the TZM-bl pseudovirus assay [26]. The ability of antibodies to bind to PIP to neutralize in the PBMC assay is particularly interesting because phosphoinositides, including PIP, are important constituents of the HIV-1 lipid bilayer and phosphoinositides are enriched in the HIV-1 envelope lipid bilayer when compared with the plasma membranes of target and host cells [27].
In the present work, by using a widely employed, clinically acceptable, well tolerated, and potent antigen– adjuvant formulation [28–32], we have produced multi-specific neutralizing mAbs that simultaneously bind to lipids, including PIP, and also to peptides that either encompassed the complete core MPER-binding speci­ficity of 2F5 or part of the core-binding specificity of 4E10. The ease of production of these mAbs demon­strates that multispecific neutralizing antibodies can be induced in a potential vaccine formulation.

v
Title: Re: Could this be the holy grail ?
Post by: veritas on September 05, 2009, 10:31:05 am
Keystone report:

http://www3.niaid.nih.gov/topics/HIVAIDS/Research/vaccines/reports/Keystone2009.htm



"With these insights, investigators hope to construct an immunogen that stimulates a neutralizing antibody response"

v
Title: Re: Could this be the holy grail ?
Post by: veritas on September 05, 2009, 04:29:01 pm

The link has been found between the potent antibodies PG9 and PG16 and anti-ps. Follow the story:

The PG9 and PG16 antibodies were discovered by research spearheaded by IAVI  ( The International AIDS Vaccine Initiative) as reported here on AIDSMED and first posted by Carlos3000 on this thread on Sept 3. The link from that post:



http://www.positivelypositive.ca/hiv-aids-news/IAVI-Two_New_Antibodies_Found_to_Cripple_HIV.html

IAVI is part of the Global Aids Vaccine Initiative.

CHAVI is researching anti-ps as part of their quest for a cure and a vaccine. They brought in Dr. Philip Thorpe's lab as part of their consortium:

http://humanvaccine.duke.edu/modules/haynes_vdc/index.php?id=2

Dr.Thorpe is the "father" of anti-ps.

In 2008, CHAVI and IAVI  joined to collaborate on HIV vaccine research and to focus on four key areas. One of those focus areas was:

"Examining the possible reasons why some people who are exposed to HIV do not progress to AIDS"



http://www.medicalnewstoday.com/articles/104371.php

Couple all the above, with J220's link, showing that liposomes  (phosphalipids) can induce antibodies:


http://www.sciencedaily.com/releases/2009/09/090901143319.htm

We have the connection !!!!!

IT'S HAPPENING !!!!!!

v
Title: Re: Could this be the holy grail ?
Post by: leit on September 06, 2009, 01:17:33 am

IT'S HAPPENING !!!!!!

Yes, your sci-fi delirium. So what else is new?

Title: Re: Could this be the holy grail ?
Post by: sensual1973 on September 06, 2009, 01:43:43 am
its like taking a pill of Xanax to feel good.
discussing something that is not even in Phase 0 .
Title: Re: Could this be the holy grail ?
Post by: leit on September 06, 2009, 02:42:22 am
its like taking a pill of Xanax to feel good.

More than one and not exactly Xanax, one would say...

Quote
discussing something that is not even in Phase 0 .

Please note also that the DONOR HIMSELF "did not benefit appreciably from the antibodies [PG9 and PG16, that make him an 'elite neutralizer' - LOL]" (http://www.sciencemag.org/cgi/content/full/325/5945/1195)!!!
Title: Re: Could this be the holy grail ?
Post by: veritas on September 06, 2009, 04:58:13 am

leit,

I seee your back to reading this thread. You couldn't stay away? I also see that your understanding of the science is still muted about the advances being made by IAVI, CHAVI and the Global  Aids Initiative.
Also, I see you still don't have any amunition to counter-debate the science posted. Your no -response to Inchlingblue's Tag-link and your response here for emotional yuks shows your colors. If you believe that this thread is science fiction, there is a simple solution------ DON'T READ IT!
I await with bated breath your next utterance!

v

Title: Re: Could this be the holy grail ?
Post by: veritas on September 06, 2009, 05:06:35 am

The NIH shows the structure of HIV:

http://www3.niaid.nih.gov/topics/HIVAIDS/Understanding/Biology/structure.htm

And also, the replication cycle:

http://www3.niaid.nih.gov/topics/HIVAIDS/Understanding/Biology/hivReplicationCycle.htm

Look at the targets!

v
Title: Re: Could this be the holy grail ?
Post by: tommy246 on September 06, 2009, 05:47:36 am
Veritas this is very exciting news keep up your excellent work keeping us all informed i am an optimist and a realist and feel were getting close.
Title: Re: Could this be the holy grail ?
Post by: veritas on September 06, 2009, 08:13:01 am

tommy246,

Thanks for your post. I believe within the next two months a lot of what I posted on this thread will become a lot clearer.
 I'm following this reseach as close as I can and I thank a lot of the members here who have found and contributed information that I have missed. At the very least, this thread shows the Global co-operation that is happening with respect to HIV research, something that should have been done 20 years ago.

I,like you, am an optimist and what really intrigues me about this research is the new anti-ps paradigm which uncloaks the virus from the immune system. The findings of more potent killer antibodies will be,I believe, the  perfect coupling with anti-ps to do damage to the virus.

Never, ever,ever give up. I'll follow this research to it's logical conclusion.

"The wok goes on!"

v
Title: Re: Could this be the holy grail ?
Post by: xman on September 06, 2009, 11:13:39 am
.
Title: Re: Could this be the holy grail ?
Post by: brazilianman on September 06, 2009, 11:29:18 am
 :'(

worst of human beings.
no shine and want to delete the brightness of others.
no hope and want the others have not.
not faith and ridicules the faith of others.


 :'(
Title: Re: Could this be the holy grail ?
Post by: georgep77 on September 06, 2009, 01:04:46 pm
veritas wants to enter the guiness book. he continues until the release of this one counting more than 2 billion replies on this thread of course all from himself to be awarded for the longest internet thread ever made.
To:  "Justice League" super friends: super xman & wonder leit

veritas ur thread is awesome, don't give up.
Title: Re: Could this be the holy grail ?
Post by: leit on September 06, 2009, 07:02:50 pm

:'(

worst of human beings.
no shine and want to delete the brightness of others.
no hope and want the others have not.
not faith and ridicules the faith of others.


 :'(

Oh, original BRAZILIAN MACUMBA!!! What a fright. ROTFL!

Title: Re: Could this be the holy grail ?
Post by: anniebc on September 06, 2009, 07:16:53 pm
Leit/Xman

If you don't agree with anything Veritas has to say or have nothing constructive to say then stay away from his thread..ridiculing other posters is not allowed, and childish behaviour is just, well...childish.

So unless you have somthing to say that has anything to do with the subject being discussed here then stay out of this discussion.

Jan

Title: Re: Could this be the holy grail ?
Post by: brazilianman on September 06, 2009, 07:25:46 pm
leit

is not voodoo. is a tragic conclusion. not like the veritas writes. simply not read. very like.
Title: Re: Could this be the holy grail ?
Post by: leit on September 06, 2009, 07:32:23 pm

veritas ur thread is awesome, don't give up.

"veritas" who??? "The Pied Piper of Hamelin"? And are you a rat or a child? ROTFL!

Title: Re: Could this be the holy grail ?
Post by: anniebc on September 06, 2009, 07:39:42 pm
Concider this a warning Leit.

Just in case you missed my last post to you here it is again:

Quote
Leit/Xman

If you don't agree with anything Veritas has to say or have nothing constructive to say then stay away from his thread..ridiculing other posters is not allowed, and childish behaviour is just, well...childish.

So unless you have somthing to say that has anything to do with the subject being discussed here then stay out of this discussion.

Jan
Title: Re: Could this be the holy grail ?
Post by: leit on September 06, 2009, 07:44:34 pm

unless you have somthing to say that has anything to do with the subject being discussed here then stay out of this discussion.

Has the following "Science" editorial nothing to do with the subject (please note uppercase bold)?
----

Science 4 September 2009
Vol. 325. no. 5945, p. 1195


POTENT HIV ANTIBODIES SPARK VACCINE HOPES

Jon Cohen

If HIV/AIDS researchers had a wish list, at the very top would sit a vaccine that could teach the body to make potent antibodies against the many strains of the virus. Despite 25 years of effort, no such vaccine is in sight, but now they are a step closer. A large team of researchers has identified the most powerful, broad-acting antibodies yet against multiple strains of the virus.

Finding good antibodies is a far cry from developing a vaccine that prods the immune system to produce them. But "broadly neutralizing antibodies" (bNAbs) are rare: Researchers have identified only a half-dozen to date. Now an international group funded mainly by the International AIDS Vaccine Initiative (IAVI) has discovered two new ones that have an unusual potency. "This has actually made me quite optimistic-for once," says Dennis Burton, an immunologist at the Scripps Research Institute in San Diego, California, who led the research effort.

For many years, Burton says, he thought that if an antibody had a broader reach, it inevitably would be weaker. "I wondered whether there would be any antibody better than the ones we had," he says. "Well, these are."

Burton, his graduate student Laura Walker, and 33 other researchers report online 3 September in Science (www.sciencemag.org/cgi/content/abstract/1178746) that the two new antibodies have unusual characteristics that open new avenues of AIDS vaccine research. "It's a great paper that describes very novel antibodies," says immunologist John Mascola of the Vaccine Research Center at the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland.

The researchers first collected blood from some 1800 HIV-infected people in Africa, Asia, Europe, and North America. Using novel techniques, they identified 10% who had antibodies that could derail more than a dozen different strains of the virus. This paper focuses on one sub-Saharan African donor; THE PERSON DID NOT BENEFIT APPRECIABLY FROM THE ANTIBODIES, WHICH ARE NO MATCH FOR HIV ONCE AN INFECTION IS ESTABLISHED.

The researchers sifted through a staggering 30,000 antibody-producing B cells from the donor and isolated two monoclonal antibodies, dubbed PG9 and PG16, that could prevent infection in more than 70% of 162 viral strains tested in cell culture. Not only were they broad acting, but the antibodies worked at minute levels-a magnitude lower than the four best characterized bNAbs so far. "It's an enormous amount of work-a tour de force," says AIDS vaccine researcher Ronald Desrosiers, head of the New England Primate Research Center in Southborough, Massachusetts.

On a more sobering note, many researchers have tried to make vaccines that elicit previously identified bNAbs. "In the last 5 years, there have been intensive efforts, and no one has succeeded," Burton says.

Still, Burton and others hope that understanding the unusual way that PG9 and PG16 stop the virus will provide new leads for AIDS vaccine designers. Specifically, HIV's surface proteins attach to immune cells to establish infections. The surface proteins naturally occur in clusters of three, or trimers, and PG9 and PG16 work only against the trimer. Other bNAbs bind to trimers as well as single surface proteins, or monomers. So this suggests that if a vaccine can present the surface proteins to the immune system in the trimeric form, it may have extra punch. It might also help explain why several AIDS vaccines that contain monomeric surface proteins have performed poorly.

Wayne Koff, who heads research and development at IAVI, says PG9 and PG16 are the first of several new bNAbs that he predicts will help guide the field. In particular, researchers hope the antibodies might help crystallographers finally elucidate the structure of a trimer, which occupies another slot on the wish list. "The machine is built and ready to crank out a lot more-and it's very likely to," says Koff.
Title: Re: Could this be the holy grail ?
Post by: anniebc on September 06, 2009, 07:53:17 pm
Yes it has so I suggest you continue to stick to the subject and stop posting crap like this:

Quote
veritas" who??? "The Pied Piper of Hamelin"? And are you a rat or a child? ROTFL!

OR THIS

Quote
Oh, original BRAZILIAN MACUMBA!!! What a fright. ROTFL!

Jan
Title: Re: Could this be the holy grail ?
Post by: GNYC09 on September 06, 2009, 07:56:27 pm
Oh, original BRAZILIAN MACUMBA!!! What a fright. ROTFL!

This comment is absolutely racist!  I'm surprised it's not deemed worthy of an immediate ban, particularly since Leit has repeatedly disparaged another member - one that actually contributes valuable information might I add. Admins, please reconsider.
Title: Re: Could this be the holy grail ?
Post by: anniebc on September 06, 2009, 08:41:55 pm
"The word "macumba" is frequently used in Brazil to refer to any ritual or religion of African origin (as slang), and although its use by non-practitioners remains largely pejorative in intent (referring to all sorts of religious (or otherwise) superstitions and luck-related rituals and beliefs), and is considered offensive"

Leit This is your final warning, any more negative post's from you will result in a TO...and an apology to Brazillianman wouldn't go amiss either.

Jan
Title: Re: Could this be the holy grail ?
Post by: leit on September 07, 2009, 02:57:23 am

"The word "macumba" is frequently used in Brazil to refer to any ritual or religion of African origin (as slang), and although its use by non-practitioners remains largely pejorative in intent (referring to all sorts of religious (or otherwise) superstitions and luck-related rituals and beliefs), and is considered offensive"

"...its use among actual practitioners is not viewed negatively. In Brazil one can find expressions such as "chuta que é macumba!" ("kick it out, it is witchcraft!") to show disagreement with bad luck." (http://en.wikipedia.org/wiki/Macumba, your source). So, nothing offensive.

Besides that, what about having been described as "worst of human beings (etc. etc.)" (http://forums.poz.com/index.php?topic=22113.msg354691#msg354691)?

Sorry, Jan, but your intervention is very biased.

Title: Re: Could this be the holy grail ?
Post by: veritas on September 07, 2009, 04:14:27 am
 After that short juvenile interruption and speaking of antibodies, it seems the boys at Duke have found and tested more potent anti-lipid antibodies and reported their findings at the aids vaccine 2008 conference. See:

http://www.hivvaccineenterprise.org/conference/archive/2008/Presentations/Thursday/Rapporteurs/1250%20R%20Pantophlet.pdf

The AIDS Vaccine 2008 Conf. was primarily focused on basic research. Much of this was dealing with broadly-neutralizing anti-HIV antibodies. The few, rare, known familiar suspects: 2F5, 2G12, b12, were the subject of hundreds of experiments presented at the conference. It seemed that "the way forward" was thought to be via insights into these promising antibodies, 2 of which bind a lipid and the virus, and one of which (b12) binds a sugar that coats a viral protein. According to other interesting data presented at the conference, the antibody b12 is apparently the most potent of the three. Along comes Duke University's researcher [Dr. Tony Moody], and presents data from CHAVI 005 experiments, showing that they've got an antibody [PPHM-Duke Collab. mab ‘PGN632’, aka ’11.31’] which only binds a lipid. This particularly potent antibody is orders of magnitude more potent than even b12, and in subtype-C HIV viruses, ( a very common subtype), the anti-lipid antibody was over 1000 times more potent than b12, 2F5, and 2G12. If that is not enough of a surprise to the field, to continue the out-of-the-box theme, it turns out that this unprecedented incredibly powerful antibody works by sticking to a lipid on uninfected T cells, causes an increase in the beta chemokines that block the CCR5 receptor, which prevent HIV from entering a cell in the first place.
Pease notice the graphs.
And I wonder what will be discussed here:

AIDS Vaccine 2009 Paris Oct 19-22, 2009
Oct 20
14:00 - 14:25 Regulation of Broadly Neutralizing Antibody Responses: The Initial B Cell Repertoire To HIV-1 Envelope
Barton Haynes, Duke University Medical Center, USA

IT"S HAPPENING!

v
Title: Re: Could this be the holy grail ?
Post by: anniebc on September 07, 2009, 05:32:49 am
"...its use among actual practitioners is not viewed negatively. In Brazil one can find expressions such as "chuta que é macumba!" ("kick it out, it is witchcraft!") to show disagreement with bad luck." (http://en.wikipedia.org/wiki/Macumba, your source). So, nothing offensive.

Besides that, what about having been described as "worst of human beings (etc. etc.)" (http://forums.poz.com/index.php?topic=22113.msg354691#msg354691)?

Sorry, Jan, but your intervention is very biased.

Leit..don't get into a pissing contest with me, I'm not in the mood and you will not win...so either stop the name calling and the insults or stay out to this thread, it's your call...end of story I'm done with you.

Title: Re: Could this be the holy grail ?
Post by: veritas on September 07, 2009, 09:58:15 am
Oh! By the way, if you read my last post concerning anti-lipid antibodies blocking the  CCR5 entry point for HIV. Perhaps you were worried about the X4 entry point? Don't be worried, be happy! Researches have found more anti-lipid antibodies that block X4.  Warning-- this is a long technical read - only for those who are really interested. Don't worry, It's not SCI-FI, IT'S HAPPENING!


http://www.jlr.org/cgi/rapidpdf/jlr.M000372v1.pdf



v
Title: Re: Could this be the holy grail ?
Post by: xman on September 07, 2009, 01:21:18 pm
I said many times that veritas is making a good job and I know he is doing so for the hope and the relief of everyone here but I sincerely don't understand why he is posting any single step in the progress of this research. Many of the documents are so technical and complicated to be absolutely impossible to understand. A lot of numbers and theories.

Wouldn't it be much easier and better to post only the results from the various conferences which are made every year to have a summary of all this studies? I'm not studying science or medicine so as an infected person i'm only interested in new drugs which treat our disease. The process to make this drug is indeed interesting but honestly not as useful, at least for me.

It's happening. Yes, great. The question remains when? The moderators should inform that those possible treatments are not just behind the corner and that many years would pass until we may use them.
Title: Re: Could this be the holy grail ?
Post by: Inchlingblue on September 07, 2009, 01:37:20 pm
I said many times that veritas is making a good job and I know he is doing so for the hope and the relief of everyone here but I sincerely don't understand why he is posting any single step in the progress of this research. Many of the documents are so technical and complicated to be absolutely impossible to understand. A lot of numbers and theories.

Some people like to know the step-by-step process not only the (voila!) final result!

Please don't take this the wrong way because I don't mean it in a bad way but I don't understand why you read this thread if you have so many problems with it. There are threads on these forums that I don't like or I am not interested in and I simply ignore them.

The moderators should inform that those possible treatments are not just behind the corner and that many years would pass until we may use them.

Why should the moderators do that? You are underestimating the readers of these forums. Just because someone is interested in following the science of HIV does not automatically mean that  they think there will be a cure tomorrow or next week (or ever). Give people a little credit. ;)
Title: Re: Could this be the holy grail ?
Post by: xman on September 07, 2009, 01:38:45 pm
Leit/Xman

If you don't agree with anything Veritas has to say or have nothing constructive to say then stay away from his thread..ridiculing other posters is not allowed, and childish behaviour is just, well...childish.

So unless you have somthing to say that has anything to do with the subject being discussed here then stay out of this discussion.

Jan



anniebc,

I'm just expressing my scepticism and the fact that this are preclinical studies which mean that they are not even in clinical trials. I'm a bit surprised that the moderators only post in this threads to warn or remember the rules of the forum which is certainly their job but I would appreciate an opinion from you or the more expert members and moderators on this studies and developments.

Most of the members probably don't know the timeline of clinical trials. Moderators should also inform and warn the members that this possible treatments are still out of range and not available for many years.
Title: Re: Could this be the holy grail ?
Post by: xman on September 07, 2009, 01:51:27 pm
Why should the moderators do that? You are underestimating the readers of these forums. Just because someone is interested in following the science of HIV does not automatically mean that  they think there will be a cure tomorrow or next week. Give people a little credit. ;)

please don't missunderstand me but also less expert people read those threads since we are in a public forum. those readers probably don't know that this are studies and not meds near approval. the entusiasm about this one is a bit exaggerated.
Title: Re: Could this be the holy grail ?
Post by: veritas on September 07, 2009, 02:38:01 pm

xman,

I'm going to try to explain to you my motives for following this line of research so closely, since you finally asked in a civil, non-anxiety ridden tone. I believe you are fairly recently infected (correct me if I'm wrong). I understand the fear when someone is newly infected. I, also, understand the sense of urgency that the newly infected have for a kinder and gentler therapy and the longing for a cure. Everyone on this thread has been waiting for a cure in some cases over 25 or more years. Think of the terror that a lot of our members have been through (including myself since 1991) when your Doctor tells you there are no medications or AZT is the only therapy I can give you and if your virus mutates......
thats terror. Couple that with researchers fighting over who was the first to find the virus rather than co=operating to find more therapies to combat the disease while all your friends die around you. That's terror! I'm not minimizing your concerns when I write this, but if one is infected today there are plenty of medications available without the horrible AE's of years past. To long term survivors, your sense of urgency, although understandable, can be trying.
Now to this thread. I've mentioned many times here that I believe anti-ps, being a new way to attack the virus (a new paradigm), has the potential to be the breakthrough we have all been waiting for since its' target is a non-mutatable portion of the virus. The global co-operation, with respect to the advancement of this therapy, is simply amazing!
Do I know for eure that this therapy is what we all have been waiting for? Of course not,only the completion of the clinical trials will tell us that. Most of the other therapies(not all) are me too drugs going after the same target --- the virus it self. For the past 25yrs the virus has always been able to outsmart the direct attack by mutating. If anti-ps works,the virus will have no defense, since the target is non-mutatable. Perhaps "The Holy Grail". I'll follow this research to lts' conclusion and should the grail be elusive, i'll close this thread and go on to the next best possibility.

But as for now "IT'S HAPPENING! "

 I hope you now understand my motives.

v
Title: Re: Could this be the holy grail ?
Post by: brazilianman on September 07, 2009, 03:19:39 pm

veritas

good history of life.
you are a survivor.
like a lot of people like you.
'm the same.


this is anti-lipid?

Sugary Achilles' Heel Raises Hope For Broad-Acting Antiviral Drugs

http://www.sciencemag.org/cgi/content/summary/325/5945/1200-a 

sorry bad English
Title: Re: Could this be the holy grail ?
Post by: xman on September 07, 2009, 03:41:41 pm
veritas,

I never doubt about the reasons of your entusiasm in this study and the theory for now indicates a high rate of success. However since this is still preliminary wouldn't it be more wise to concentrate our attention to those possible treatments in advanced clinical testing? I for example have big hope in the Virxsys candidate. It is now in phase II clinical testing and received fast track status from FDA. At least we have here more hope to see something in the next years than this alternative about monoclonal antibodies. Since this is a complicate issue more research is needed and this will take years.

To your comments about me, yes I was infected relatively recently and I fear everyday about the things to come. I know the meds used to today but there are still unknown long term toxicities which deserve concern. Lipodystrophy for example isn't yet totally eliminated even if the new meds are not directly linked to it. If it wouldn't be for the toxicities an immediate begin for treatment would be recommended but we still need to balance the effectiveness of this meds against the possible side effects.

We need better treatments and we need them soon. We can't wait anymore. I'm not on treatment yet but I don't know for how long. This new approaches are great but they are too far away for practical applicance. I'm reading horror stories about those who have developed resistance to much of the meds and those who have initial signs of lipoatrophy after only a few years of treatment. Others needs to stop because unable to live a normal life. This is a sign that the current meds have huge limitations and it makes me angry that in all this years for complacenty low improvement was archieved.

It surprises me even more that after all the disappointments in HIV research over the recent years so much optimism is still around. Many here are very skeptical like me that something potent will pan out soon and the reason is that for years we're hearing that the cure is far away and perhaps never available. It is upsetting and all this entusiasm about new findings when in the meantime hundreds of infected are dying due to the lack of medicines.
Title: Re: Could this be the holy grail ?
Post by: georgep77 on September 07, 2009, 05:04:09 pm
I for example have big hope in the Virxsys candidate. It is now in phase II clinical testing and received fast track status from FDA.
I respect & understand your point of view xman, perhaps you can begin a new thread about virxsys.

                         :)
Title: Re: Could this be the holy grail ?
Post by: veritas on September 07, 2009, 05:04:37 pm

xman,

I can see from your response, that perhaps you don't reaaly know how these forums and threads work
This forum is dedicated to reseach. This particular thread which I started is dedicated to anti-ps, because that is the research I am interested in. If this research is not giving you what you need, then there are a number of things you can do:
1. Do your own research.

2. Start your own thread.

3. Go to another thread more in-line with your interests.

4. Read about the latest treatment news provided by Aidsmeds.

5. Go to other sights  and read their news.


As far as this thread is concerned, I am only going to post about research concerning anti-ps. I ask that  you do the same if you come to this thread. Again, if this research doesn't interest you then this thread is not for you. I am not going to discuss this any further.

v
Title: Re: Could this be the holy grail ?
Post by: veritas on September 07, 2009, 05:12:36 pm

brazilianman,

I don' believe that is anti- ps. There was not enough information for me to follow-up.

v
Title: Re: Could this be the holy grail ?
Post by: veritas on September 08, 2009, 12:53:50 pm

By the way, how's Bavituximab doing on the cancer front? How about nearing completion in Phase 2 !!!
This shows Bavituximab is not only safe in humans to this point, but also it's method of action (which is the same for anti-viral) is showing efficacy. Is it happening for cancer? You bet!!!

http://finance.yahoo.com/news/Peregrine-Pharmaceuticals-prnews-4025018256.html?x=0&.v=1

Bring on the anti-viral news!

v
Title: Re: Could this be the holy grail ?
Post by: veritas on September 10, 2009, 09:22:03 am

Anti-ps antibodies ----- Many applications

http://www.medscape.com/viewarticle/587338

"The current paradigm of aPL holds that they are important in thrombosis, but they may have much wider clinical significance"

A long read  and overview (somewhat technical) ------ with potential far reaching benefits! (hiv is mentioned)

v
Title: Re: Could this be the holy grail ?
Post by: Inchlingblue on September 10, 2009, 10:51:54 am
v: the link goes to a login page
Title: Re: Could this be the holy grail ?
Post by: veritas on September 10, 2009, 01:18:56 pm

Inch,

Sorry about that ----  Here's the abstract.

Antiphospholipid Antibodies: Paradigm in Transition
Lawrence L. Horstman; Wenche Jy; Carlos J. Bidot; Yeon S. Ahn; Roger E. Kelley; Robert Zivadinov; Amir H. Maghzi; Masoud Etemadifar; Seyed Ali Mousavi; Alireza Minagar


Published: 03/18/2009

Abstract
Objectives: This is a critical review of anti-phospholipid antibodies (aPL). Most prior reviews focus on the aPL syndrome (APS), a thrombotic condition often marked by neurological disturbance. We bring to attention recent evidence that aPL may be equally relevant to non-thrombotic autoimmune conditions, notably, multiple sclerosis and ITP.
Organization: After a brief history, the recent proliferation of aPL target antigens is reviewed. The implication is that many more exist. Theories of aPL in thrombosis are then reviewed, concluding that all have merit but that aPL may have more diverse pathological consequences than now recognized. Next, conflicting results are explained by methodological differences. The lupus anticoagulant (LA) is then discussed. LA is the best predictor of thrombosis, but why this is true is not settled. Finally, aPL in non-thrombotic disorders is reviewed.
Conclusion: The current paradigm of aPL holds that they are important in thrombosis, but they may have much wider clinical significance, possibly of special interest in neurology.


v
Title: Re: Could this be the holy grail ?
Post by: veritas on September 10, 2009, 01:27:40 pm
Relevant paragraph to HIV from above article:

HIV/AIDS
A viral cause of APS has been proposed.[318] HIV infection carries a high frequency of aPL[34,319] but here, too, the aPL in HIV were considered to be of the infection-related type and non-pathogenic. Haynes et al[46] point out that anti-HIV antibodies mounted by most patients fail to neutralize the virus, but a rare few do mount neutralizing responses, and those studied turned out to be polyspecific aCL, similar to the aPL profile seen in lupus (SLE). Indeed, they cite references indicating that SLE patients appear to be protected against contracting HIV, and argue that the general population fails to make such aPL because they have been deleted from the repertoire as self-reactive. In support of their contention, one of the neutralizing anti-HIV they studied was autoreactive with dsDNA, centromere B, histones and other self targets.[46] Relatedly, Zhang et al[320] investigated why most people fail to mount effective immune responses to HIV envelope proteins (Env), and suggested that Env suppresses CD40L expression, which in turn blunts the T cell ability to activate DCs. However, we feel that findings of Zhang et al[320] are consistent with the scenario given by Haynes et al.[46] Specifically, the aPL seen in the context of HIV and other infections may be more than epiphenomena and could offer important clues to immune function.

 
v
Title: Re: Could this be the holy grail ?
Post by: veritas on September 23, 2009, 08:50:07 am

What will be discussed at these symposiums in Paris next month?

AIDS Vaccine 2009 - Scientific Program

Symposium 2: Generation of Antibody Responses and Diversity

Regulation of Broadly Neutralizing Antibody Responses: The Initial B Cell Repertoire To HIV-1 Envelope
Barton Haynes, Duke University Medical Center, USA

Broadly neutralizing anti-HIV-1 antibodies disrupt a hinge-related function of gp41 at the membrane interface
Likai Song,Dana-Farber Cancer Institute, USA

Symposium 6: Refining Immunogen Design

Structural basis of broad neutralization of HIV-1
Ian Wilson, The Scripps Research Institute, USA

Plenary Session 3: B Cell Biology

Development of anti-HIV antibodies in humans with high titers of broadly neutralizing antibodies
Michel Nussenzweig, Howard Hughes Medical Institute, The Rockefeller University, USA

Closing Session

Are we targeting the right HIV determinants?
Françoise Barré-Sinoussi, Institut Pasteur, France

v
Title: Re: Could this be the holy grail ?
Post by: veritas on September 23, 2009, 09:06:44 am

In my previous post, look for PGN632  in Paris ------- Remember this?

http://www.cavd.org/Lists/Conference_Abstracts/DispForm_Custom.aspx?List=1509afcc%2D36c2%2D4e00%2D96cb%2D6d344366a502&ID=5

Why so quiet about this antibody?
What has been happening for the past year?
Stay tuned ........!

v
Title: Re: Could this be the holy grail ?
Post by: veritas on September 23, 2009, 09:32:26 am

For those of you who do not remember the background of the PGN antibodies, here's a little history:

http://www.earthtimes.org/articles/show/studies-presented-at-aacr-annual,792469.shtml

"Dr. Xianming Huang, assistant professor of pharmacology at UT Southwestern Medical Center and lead author of the study, noted, "Dendritic cells are the professional antigen-presenting cells of the immune system and they play a crucial role in initiating adaptive immune responses. Dendritic cells must be mature, or activated, to be effective, yet tumors and other pathogens such as viruses often possess the ability to undermine this maturation, thereby suppressing the immune response. The results presented today suggest that by blocking exposed PS, anti-PS antibodies have the potential to promote dendritic cell maturation in the body and thereby stimulate a more effective immune response"

Is it Happening ??????

v
Title: Re: Could this be the holy grail ?
Post by: veritas on September 25, 2009, 09:56:24 am

Speaking of research ---- Does Poxvirus utilize PS?   YUP!!!

http://www.pnas.org/content/early/2009/09/23/0909376106.abstract?sid=b7e7b186-3492-4dbc-b6c8-69df58d7e0ec

Another potential target !

IT'S HAPPENING !!!

v
Title: Re: Could this be the holy grail ?
Post by: veritas on October 05, 2009, 08:27:09 am

Anti-ps, Bavituximab, shows positive results in Phase 2 lung cancer !

http://finance.yahoo.com/news/Peregrine-Pharmaceuticals-prnews-1354732101.html?x=0&.v=1

Lung cancer is one of the most difficult cancers to treat.


Recent analysis from the 21-patient cohort now shows the median progression-free-survival (PFS) for these patients was 6.5 months, which compares favorably with the PFS range of 4.2 to 4.5 months reported in a similar patient population receiving carboplatin and paclitaxel as a single agent in NSCLC trials that were the basis for the design of the ongoing bavituximab study. Peregrine also reported that it has completed enrolling the total of 49 NSCLC patients planned for this study.

v
Title: Re: Could this be the holy grail ?
Post by: veritas on October 07, 2009, 09:37:38 am
How many collaborations are studying anti-ps?   See here:

Supplement 1: Master List of Peregrineʼs Infectious Disease PS Targeting Collaborations (scroll down to view HIV collaborations)

http://www.peregrineinc.com/index.php?option=com_content&task=view&id=87&Itemid=153

St.Georges  Medical School  in London is one of the major collaborators in the study of HIV.

Do any of our UK friends know St. Georges ? I wonder why so many 1st class medical centers are researching anti-ps ? Why is the Gates Foundation pouring research funds into anti-ps?

WHY?  Because ----------

Anti-ps  -----  It's Happening !!!

v
ps: please notice most research is in chronic infection !
Title: Re: Could this be the holy grail ?
Post by: veritas on October 07, 2009, 10:06:19 am

Could it be that with all the research going on with anti-ps as an anti-viral that a company must form a team to keep track of it all ?  Yup!

http://finance.yahoo.com/news/Peregrine-Pharmaceuticals-prnews-517780487.html?x=0&.v=1

Is it Happening?  You bet!


v
Title: Re: Could this be the holy grail ?
Post by: freewillie99 on October 07, 2009, 12:24:32 pm
You bet!

Shouldn't that be "You betcha"?

Wasilla Willie
Title: Re: Could this be the holy grail ?
Post by: veritas on October 07, 2009, 12:51:34 pm

This link shows where anti-ps is being studied as a therapy:

http://www.peregrineinc.com/index.php?option=com_content&task=view&id=84&Itemid=150

•Peregrineʼs PS targeting antibodies are now under investigation as potential therapy for chronic HIV infection at leading HIV research centers in the U.S. and U.K. Data presented by Duke University scientists at the international AIDS Vaccine.

Is it happening?  You betcha!  ( For you Free! )

v
Title: Re: Could this be the holy grail ?
Post by: datdude on October 07, 2009, 06:46:37 pm
I'm confused, is anti-ps supposed to cure hiv, can vertas give me a simple explanation of what anti-ps is supposed to do to hiv. Thanks
Title: Re: Could this be the holy grail ?
Post by: J220 on October 07, 2009, 07:13:15 pm
I'm confused, is anti-ps supposed to cure hiv, can vertas give me a simple explanation of what anti-ps is supposed to do to hiv. Thanks

Are you kidding? There's 10 pages in the thread, surely you can find the answer somewhere there.....
Title: Re: Could this be the holy grail ?
Post by: datdude on October 08, 2009, 05:32:08 pm
I see things about cancer but no I'm not kidding, I don't have time to read through 10 pages of information, I'm just wondering exactly what anti-ps could do to Hiv, and I wasn't asking you for a smart remark, I was asking veritas for a simple answer since he knows so much about anti-ps.  :o
Title: Re: Could this be the holy grail ?
Post by: Inchlingblue on October 08, 2009, 07:10:43 pm
I see things about cancer but no I'm not kidding, I don't have time to read through 10 pages of information, I'm just wondering exactly what anti-ps could do to Hiv, and I wasn't asking you for a smart remark, I was asking veritas for a simple answer since he knows so much about anti-ps.  :o

I guess it comes with the territory that when there's a long-standing, popular thread that gets regularly updated with new information there will be those that miss what came before and it becomes daunting to read the whole thread.

There are sections in the thread that contain the answers to what you're asking. I can't find them right now but I know they're there, lol.
Title: Re: Could this be the holy grail ?
Post by: carpediem98 on October 09, 2009, 12:09:56 am
Here's an answer I gave to a similar question a while back... it's not COMPLETELY what you're looking for, but it's a good quick primer on anti-PS for anti-viral purposes:

Quote
My understanding of the principle is this.  HAART doesn't impact resting cells containing HIV because every drug involved in HAART acts directly against a specific activity of the virus - the virus is going to copy its RNA, or it's going to insert a double-stranded DNA into that of a host cell, or it's going to chop up a strand of DNA to begin budding, etc.  HAART directly intervenes, and if the cell is resting, HIV can't be interrupted while it tries to do any of those things because it isn't trying to do any of those things.

Anti-PS, howerver, doesn't act against an active virus, but against a compound on the outside of any cell containing a viral particle, whether it's "awake" or "asleep."  The reason for this would be that the cell begins to show signs of damage once it is compromised by the virus's entry.  At that point, the phosphatidylserene (PS) flips and is on the outside, and the cell appears to the rest of the immune system to be a normally dying cell rather than an infected, otherwise "normal" cell.

It might take repeat dosings to get it into all the nooks and crannies of the body, but eventually - theoretically - the anti-PS drug will have coursed throughout the body, and as it goes along, it will encounter these resting cells along with all the active, infected cells.  The resting cells, when they "wake up," will enter the bloodstream already marked for deletion as an "unwelcome invader."  HIV will not have a chance to replicate because the cell will be marked for destruction immediately upon waking up.  Theoretically, then, anti-PS has the POTENTIAL to be a treatment that would eradicate HIV as anything but a harmless, resting passenger.
Title: Re: Could this be the holy grail ?
Post by: veritas on October 09, 2009, 05:50:24 am

datdude,

Here you go:


HIV - Phosphatidylserine Breakthrough









The July announcement by NIAID Director Dr. Anthony Fauci to scrap the upcoming "PAVE-100" HIV vaccine clinical trial, (following on the heels of the failed Merck "STEP" HIV vaccine trial), showed yet again how difficult and elusive the goal of an effective HIV vaccine remains.

In the midst of these sobering developments, an important new insight was gained into why experimental HIV vaccines have failed to elicit an adequate immune response. The discovery, published in the August issue of the Journal of Virology (1), came from the leader of NIAID's “CHAVI” organization, Dr. Barton Haynes of Duke University, who is also a principle investigator of the Gates Foundation HIV vaccine effort.

In their paper, Haynes and colleagues discuss experiments showing that HIV weakens the immune system much faster than previously thought. The primary mechanism responsible for this immunosuppression is an overwhelming amount of what Haynes terms "microparticles", which are tiny particles shed from the outer membranes of infected and dying cells. This cellular debris accumulates during early HIV infection, and circulates throughout the body blunting the functions of the immune cells that would ideally fight the virus. Popular news articles have discussed this aspect of the Duke researchers' findings, but the details and broader implications of the team's discovery have yet to be elucidated in the media.

The paper explains that the microparticles contain the molecule phosphatidylserine (PS) exposed on their surface. PS is a lipid that normally lines the interior of the cell membranes of every cell in our body. As a cell dies, it loses the ability to maintain PS on the inside of the cell membrane. The PS flips to the exterior, where it is perceived by immune cells as a sign of a dying native cell. The Haynes team cite recent data showing how exposed PS appears to be the fundamental signal that shifts the behavior of immune cells into not mounting an antigen-specific attack, since PS is interpreted as a sign of “self” rather than a foreign invader (2). Other researchers have also recently illustrated the suppressive effects of PS on macrophages, the resulting cytokine environment, dendritic cells, and T cells (3-7). It is thus no surprise that recent research has also revealed exposed PS as a feature common to many diverse pathogens (8-22), as if they independently evolved to exploit a similar mechanism of evasion, since it provides the crucial advantage of triggering an inappropriate immune response, facilitating the pathogen's survival and proliferation.

A review of Haynes' recent patent applications provides further details that have yet to be published in the journals. In one application, titled “Multicomponent Vaccine” (23), Haynes explains that any future successful HIV vaccine must interrupt this PS-mediated immunosuppressive signaling. A specific goal mentioned is for a vaccine to induce antibodies to PS (anti-PS), thereby blocking the overwhelming immune suppression seen in the Duke research, allowing the viral immunogen in the vaccine the chance to evoke T and B cells which effectively fight the virus.

In yet another recent patent application, Haynes proposes using anti-PS as a promising treatment for people already infected with the virus (24). He discusses the ability of anti-PS monoclonal antibodies to bind to HIV and HIV-infected cells, saying anti-PS "can be safely used as a therapeutic Mab for treatment of HIV infected subjects", and that it can "broadly neutralize HIV in an unprecedented manner".


Perhaps the most fascinating comment found in one of Haynes' many recent patent applications is his suggestion that HIV's method of immune evasion may be a general escape mechanism utilized by other pathogens (24), and that similar means of therapy may be effective against other diseases. Indeed, a review of the recent major journals corroborates this concept:

In April, the journal Science published experiments showing that the pox family of viruses, (vaccinia), utilize exposed PS to gain entry into cells (25).

In the March issue of the journal Clinical Cancer Research, scientists from Harvard University discuss experiments in which blocking PS signaling helped facilitate complete melanoma tumor regressions (26).

The protozoan parasites responsible for many of the deadly diseases affecting much of the developing world have been found to rely on exposed PS to successfully avoid the immune system of their host (16-22).

Several cancer researchers have recently published data which bears a striking resemblance to the new findings of the Haynes HIV group, showing a very similar method of systemic immune suppression caused by PS-exposing microparticles shed from tumor cells (29-34), (see also 27, 28).

In another recent Haynes patent application he also discusses PS-exposing microparticles as playing a role in the pathogenesis of several auto-immune diseases as well as atherosclerosis (35), (see also 36-40).




Taken together, these discoveries suggest a new immunological perspective of pathogenesis in general. A paradigm appears to be emerging in which the necessary and admirable flexibility of the immune system has been exploited precisely where it is most vulnerable – when it must commit to a 'friendly' response. The recent HIV research by Haynes and colleagues, focusing on PS-induced immune suppression, and the safe therapeutic targeting of exposed PS with antibodies, carries implications of unprecedented broad therapeutic potential.

The above is on page 1 of the thread. Carpediem gave you a good summary also. If your interested in anti-ps, take the time to read the thread. Even though it gives a lot of information as to the MOA (method of action) of anti-ps  against other pathogens and cancer, the moa is the same for all and if it works in one , it should work in all.They are farthest along in the cancer application (phase 2). The trick here is to mount a strong enough immune response for the antibody to do it's job. That's what they are testing at CHAVI.

Carpe:
Glad you started to post again. How have you been feeling? Stick around will you we miss ya!

v






Title: Re: Could this be the holy grail ?
Post by: carpediem98 on October 10, 2009, 04:15:02 pm
Thanks, V.!
I've been well - so well that I've not been online much, in fact!  I've moved to a great new home, have some wonderful things happening in my career, and have been physically well for several months now (aside from a brief visit from H1N1).

In order to keep this on-topic, here's another article about Peregrine's new anti-viral efforts - http://www.ritabiotech.com/news.html?page=1&id=293 (http://www.ritabiotech.com/news.html?page=1&id=293).  It contains this snippet:

Quote
Peregrine's anti-PS antibodies are also generating positive data in preclinical HIV studies conducted by researchers from leading universities and medical research institutions in the U.S. and U.K. with funding from the Bill and Melinda Gates Foundation and the National Institutes of Allergy and Infectious Diseases (NIAID). These studies have yielded promising results that support the potential of PS-targeting agents for use as therapeutics, in vaccines and as topical microbicides, an especially promising application urgently needed in the effort to help women avoid infection with HIV and other sexually transmitted diseases such as herpes viruses and chlamydia. In addition, collaborators are also investigating the utility of PS-targeting antibodies against CMV infections and leishmaniasis, a protozoan disease that attacks people and cattle in tropical regions, with devastating effects on both health and economic well-being.

It also has this great, concise description of the basic mechanics of anti-PS.

Quote
PS [phosphatidylserene], a lipid molecule normally found only on the inside of cell membranes, becomes exposed on the outside of the membranes of certain viruses and virally infected cells. A rapidly growing body of published scientific research confirms that exposed PS is directly involved in the pathogenesis of many serious infectious diseases. Exposed PS enables viruses to evade immune recognition and dampens the body's normal responses to infection. By masking the exposed PS, PS-targeting antibodies are believed to block these effects, allowing the body to develop a robust immune response to the pathogen. Peregrine's PS-targeting antibodies have been shown to help clear infectious virus from the bloodstream and to induce antibody-dependent cellular cytotoxicity. Researchers have found that PS is exposed on the outer membrane of cells infected with HIV, influenza, herpes simplex viruses, hemorrhagic fever viruses, measles and members of the smallpox and rabies virus families. Scientists have also found that PS is exposed in certain infections caused by protozoan organisms, such as malaria and leishmaniasis.
Title: Re: Could this be the holy grail ?
Post by: veritas on October 11, 2009, 05:54:00 am

carpe,

The indications that anti-ps is being tested for is mindboggling! When the DOD showed interest and awarded one of their largest grants for broad spectrum anti-virals to anti-ps, I realised that quite a few scientists must believe there is something fascinating here.
The cancer indication has been moving along with great results (close to phase 3). What's holding up the viral end is beyond me unless it has to do with the government. However, if there were any problems with the viral end, I'm sure all this reasearch would have been terminated ---- instead it's increasing. Makes you go -"HMMMMMMM"! Thanks for the link!

v

ps: Good luck in your new home. Glad to hear everthing is going well. H1N1--ugh! You beat it though --BRAVO !
Title: Re: Could this be the holy grail ?
Post by: leit on October 12, 2009, 08:00:49 pm

have been physically well for several months now (aside from a brief visit from H1N1).

Please forgive my OT. In your doctor's opinion, had you somehow a "different"/more serious form of H1N1 flu (because of HIV)?
Thank you!

Title: Re: Could this be the holy grail ?
Post by: brazilianman on October 22, 2009, 06:06:15 am
veritas any news of bavituximab hiv?

this study was not cron task to end months ago?
they should publish the research reports
Title: Re: Could this be the holy grail ?
Post by: veritas on October 22, 2009, 08:30:32 am

brazilianman,

Still no info on the HIV/HepC trial  They are being very quiet about the viral results in all indications. DOD seems to be in control  as far as testing goes for other viral indications and CHAVI is carrying the ball on the HIV side. However, there is more news on cancer:

http://finance.yahoo.com/news/Peregrine-drug-prompts-apf-2411616754.html?x=0&.v=1

Time will tell. ( they are being too quiet)

v
Title: Re: Could this be the holy grail ?
Post by: veritas on October 23, 2009, 05:44:16 am

A lot of information coming out of Paris. Here's a sample:

P05-04

Neutralizing antibodies induced by immunization with liposomal gp41 peptide simultaneously bind both the 2F5 or 4E10 epitope and lipid epitopes



GR Matyas1, L Wieczorek2, Z Beck2, C Ochsenbauer-Jambor3, JC Kappes4, NL Michael1, VR Polonis1, and CR Alving1



1Walter Reed Army Institute of Research, Rockville, Maryland, USA; 2Henry M. Jackson Foundation for the Advancement of Military Medicine, Rockville, Maryland, USA; 3University of Alabama at Birmingham, Brimingham, Alabama, USA; 4University of Alabama at Birmingham/Veterans Affairs Medical Center, Birmingham, Alabama, USA



Background: The purpose of this study was to produce peptide- and-lipid-induced murine monoclonal antibodies (mAbs) that replicate the characteristics of the 2F5 and/or 4E10 human antibodies for binding both to the membrane proximal external region (MPER) of gp41 and the adjacent lipid bilayer for neutralizing HIV-1 infection of CD4+ lymphocytes.



Methods: Liposomes containing both a synthetic MPER peptide (662-LELDKWASLWNWFDITNWLWYIK-684) as a peptide antigen, phosphatidylinositol-4-phosphate (PIP) as a lipid antigen, and monophosphoryl lipid A as a potent adjuvant were used as a formulation to immunize mice. MAbs were then produced and tested for binding to MPER, gp41, and PIP and for the ability to neutralize a replication-competent molecular clone of HIV-1 encoding a primary envelope protein and Renilla luciferase as reporter in human peripheral blood mononuclear cells (PBMC).



Results: Multispecific IgM MAbs were produced that bound PIP and that simultaneously bound to either the core MPER site of 2F5 or that overlapped with the 4E10 site. The mAbs also bound to negatively charged phospholipids, including cardiolipin, and lipid A. They had lipid binding specificities similar to those observed for 4E10 (Matyas et al., BBA 2009; 1788:660-5). In contrast to 4E10, these murine mAbs bound weakly to cholesterol and not to galactosyl ceramide. While these murine mAbs neutralized HIV-1 less well than 2F5 IgG, they inhibited more efficiently than the IgM isotype of 2F5.



Conclusion: This study employed widely used, clinically acceptable, safe, generic antigen-adjuvant constituents that potentially could be used for human immunization. Using liposomes containing MPER peptide and PIP as antigens and lipid A as an adjuvant for immunization, multispecific antibodies that simultaneously bind gp41 MPER and adjacent lipid and neutralize HIV-1 infection in a PBMC assay were induced. This is the first time that both the peptide and lipid binding specificities of 2F5 (or 4E10) have been induced experimentally in a neutralizing antibody

It's Happening !

v
Title: Re: Could this be the holy grail ?
Post by: J220 on October 23, 2009, 12:08:37 pm
For those of you like myself who own Peregrine stock: they just had a reverse stock split (1:5), apparently they are trying to keep their stock value up to meet NASDAQ requirments and also to attract more investors:

http://peregrineinc.com/media/siteFiles/FAQs-Reverse-Stock-Split.pdf (PDF file).

So if you saw the PPHM stock suddenly jump over 500%, no, don't go celebrating just yet, it corresponds to the split...although the stock price is up, each investor has less number of stocks, making the equity value the same...lol. Maybe soon we can celebrate, but not just yet....!
 
P.S. ticker has the "D" suffix for the next 20 days or so, then it will revert back to PPHM....standard protocol for reverse splits.
Title: Re: Could this be the holy grail ?
Post by: esper on October 23, 2009, 10:08:54 pm
I just spent the last 2 days reading this entire thread. Veritas, Inchlingblue and many others thanks for your time and effort to put the detailed links, analysis, and step-by-step progression of this research here. I'm newly diagnosed and this has given me a great education (lots of the tech details of course I don't fully understand, but I'm working on it). Of course, this is one of many avenues being explored by various reseachers, but its pretty exciting. All of this take time to research, tests, trials, setbacks, adjustments, etc....but its pretty exciting all the same. Thanks for this. Esper
Title: Re: Could this be the holy grail ?
Post by: veritas on November 04, 2009, 05:50:01 pm

Anti-ps takes another step !

http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=421983

It's still happening !

v
Title: Re: Could this be the holy grail ?
Post by: xman on November 04, 2009, 07:51:29 pm
The hcv/hiv trials was delayed for another year. Phase I will not present any results until September 2010. Is there any reason for this slow progress?
Title: Re: Could this be the holy grail ?
Post by: veritas on November 05, 2009, 04:58:41 am

xman,

The bulk of the research on anti-ps viral is being done by CHAVI and the Dept of Defense. Peregrine has limited funds themselves and are pushing the anti-cancer. The research being done by CHAVI and DOD is research that is very valuable to the anti-ps anti-viral platform and the researchers doing the work are the top infectious disease scientists in the country and the world. It will take time.

v
Title: Re: Could this be the holy grail ?
Post by: xman on November 05, 2009, 03:54:13 pm
It will take time.

v

Yes it will take time. I was reading the article about experts that warn AIDS will remain a global crisis in 2031 unless there is a more comprehensive response. It's quite bizzarre that scientists still ask for time after 3 decades. They aren't aware of the consequences if we don't move on quickly.

Read here:
http://www.poz.com/articles/aids_global_crisis_2031_1_17515.shtml
Title: Re: Could this be the holy grail ?
Post by: veritas on November 06, 2009, 05:00:31 am

xman,

It's true, the costs are not sustainable over the long term for this disease.  Thus, all the new research with respect to the global groups that are working on the problem like CHAVI with anti-ps and  the other research that can be found here on the research forum. Hopefully ,there will be a breakthrough.

v
Title: Re: Could this be the holy grail ?
Post by: J220 on November 06, 2009, 10:52:18 am
It's quite bizzarre that scientists still ask for time after 3 decades. They aren't aware of the consequences if we don't move on quickly.

Read here:
http://www.poz.com/articles/aids_global_crisis_2031_1_17515.shtml

I beg to differ, I don't think anyone is "asking" for time. It just takes time to develop these things. And I doubt any scientist or medical researcher is not aware of the magnitude of not only the present crisis but how much worse it will get if this not defeated.

But I think news such as this are necessary to keep this in the public's eye.

Getting back to anti-ps (or derivatives), Veritas did you read about this?

http://www.sciencedaily.com/releases/2009/11/091105165527.htm

Inchblue also posted on it here:

http://forums.poz.com/index.php?topic=29768.0

Seems like Peregrine has some competition! I will have to keep an eye on that one too. It does seem like validation of the methology, though (flag pathogen and let body kill it, as opposed to directly eliciting an antibody/ cellular response).

Cheers, J.
Title: Re: Could this be the holy grail ?
Post by: veritas on November 06, 2009, 02:06:22 pm

Ray,

I did read that link , but thanks for posting it here. The therapy is quite similar to anti-ps in it's mechanism of action and although I have not researched it yet, I bet the proteins being targeted are gp41 and gp120. I believe these are constant on the virus. I welcome any avenue that has the potential to lead to a breakthrough. Good one to watch. Any therapy that is going to work must get around the stealthy aspect of the virus with respect to the immune system. Let's hope one of these is it !

v
Title: Re: Could this be the holy grail ?
Post by: veritas on November 10, 2009, 09:11:03 am

Duke has anti-lipid vaccine in development:

http://www.dukehealth.org/HealthLibrary/News/scientists_explain_binding_action_of_two_key_hiv_antibodies_could_lead_to_new_vaccine_design

"The research team is already working on designing a vaccine that incorporates a lipid component.  “The demonstration of the role of virion lipid reactivity in the overall function of these neutralizing antibodies has provided key insights into what the immune system may need to see to make such antibodies”, says co-author and Vaccine Institute Director Barton Haynes. “New vaccine designs trials based on these observations are now ongoing in animals.” 

How will these antibodies attach to the virus ?:

"The 2F5 and 4E10 antibodies have unusually long, loopy protein segments that are hydrophobic, meaning that they are attracted to lipids.  The researchers found that successful docking of the antibody to the HIV outer coat membrane region required antibody attachment to HIV’s membrane, which contains lipid. "

It's Happening !





Title: Re: Could this be the holy grail ?
Post by: veritas on November 10, 2009, 12:42:41 pm

Anti-ps and Brain cancer:

http://finance.yahoo.com/news/New-Study-in-Clinical-Cancer-prnews-1276474526.html?x=0&.v=1

" Treatment in Combination with Radiation Doubled Survival Time and Produced Long-Term Cures in Lethal Brain Cancer Model -
- Confirms PS-Targeting Antibodies Have a Dual Mechanism of Action that Both Destroys Tumor Blood Vessels and Initiates a Robust Immune Response to the Tumor -
- New Studies Demonstrate Therapeutic Potential of Bavituximab in Brain Cancer In Addition to Ongoing Phase II Trials in Advanced Breast and Lung Cancers -"

It's Happening in Brain Cancer Too !

v
Title: Re: Could this be the holy grail ?
Post by: veritas on November 18, 2009, 09:44:43 am

Another step forward for anti-ps/ anti-viral:

http://finance.yahoo.com/news/Peregrine-Pharmaceuticals-prnews-3864345621.html?x=0&.v=1

It's happening !

v
Title: Re: Could this be the holy grail ?
Post by: veritas on November 22, 2009, 09:33:15 am

Duke University using results from Thai vaccine trial in quest for their vaccine:

"The latest IAVI Report details the modest protection achieved in the Thai RV144 trial. The Report also discusses the subsequent research that scientists will be performing to mine as much as possible from the available samples. In short, in the words of the report, “The Search [for correlates of immune protection] Is On”.



The scientist tasked with heading the steering committee of the overall search is Dr. Bart Haynes of Duke University. Besides helping direct the effort, Haynes’ particular project will involve the investigation of protection provided by antibodies, and not just directly neutralizing antibodies"


http://www.iavireport.org/archives/2009/Pages/IAVI-Report-13(5)-raft-of-results.aspx


v
Title: Re: Could this be the holy grail ?
Post by: veritas on November 23, 2009, 08:57:47 am
The world collaborates on anti-ps. 5 collaborators are working on HIV. The list of scientific , medical and anti-viral advisors reads like a who's who of the medical research world.

http://www.peregrineinc.com/index.php?option=com_content&task=view&id=15&Itemid=29

The above link shows the addition of Dr. Bruce Chabner----- Clinical director of Mass. General cancer center, Chief of Hematology and Oncology at Mass.General and a Professor of Medicine at Harvard Medical School. It doesn't get any better than this!

It's Happening !!!!!

v
Title: Re: Could this be the holy grail ?
Post by: veritas on November 25, 2009, 08:41:31 am

Duke University"s research moving forward another step:


http://www.ncbi.nlm.nih.gov/pubmed/19906992?itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum&ordinalpos=2

It's Happening!

v
Title: Re: Could this be the holy grail ?
Post by: veritas on December 20, 2009, 10:23:27 am

An in-depth report to the Global HIV/AIDS Vaccine Enterprise:  CHAVI

https://chavi.org/wysiwyg/downloads/Fall_Report_Enterprise_Report_(web).pdf

This report brings the global community up to date concerning the research for an HIV vaccine. The report is extensive.

For those of you who are interested in following the research closely concerning an HIV/AIDS vaccine, this extensive report focuses on what the global community is doing and how information is being shared throughout the world to reach it's goal.

A long read!

But it's Happening !


v
Title: Re: Could this be the holy grail ?
Post by: veritas on January 05, 2010, 03:10:13 pm

Latest PS research findings ------  for both cancer and viral disease:

http://www.mdpi.com/1420-3049/14/12/4892/pdf


5.2. Annexin A5 in infections
It has been shown that many viruses can induce both apoptosis and PS exposure in the infected
cells. PS can also be found in the outer membrane of enveloped retrovirus [136]. We studied the
influence of AnxA5 on chronic macrophage infection with HIV-1, known to expose PS on its surface.
We found that infectivity in human macrophages of HIV-1 was significantly reduced in the presence
of AnxA5 [131]. Zandbergen and colleagues explored the role of PS during Leishmania disease and
discovered that virulent inoculums of Leishmania promastigotes contained a high ratio of PS exposing
apoptotic parasites. However, after apoptotic parasites depletion from the virulent inoculum,
Leishmania did not survive in phagocytes in vitro losing their disease inductor capacity in vivo [107].
In summary, AnxA5-based therapy strategies may be also useful to improve immune reactions against
various infectious agents which use the PS exposure as a tool to improve their survival by fooling the
immune system as well as against apoptotic cancer cells (Figure 4).

Long read !

v
Title: Re: Could this be the holy grail ?
Post by: veritas on January 21, 2010, 08:46:31 am

Targeted therapeutics for infectious disease up-dated by Perigrine Pharmaceuticals:



http://www.peregrineinc.com/images/stories/media/siteFiles/Bavituximab%20Anti-Viral%20Fact%20Sheet%20Jan%202010.pdf

Not fantasy, it's still happening !

v
Title: Re: Could this be the holy grail ?
Post by: veritas on January 21, 2010, 09:13:24 am

Let's not forget Cancer:

http://www.peregrineinc.com/images/stories/media/siteFiles/Bavituximab%20Anti-Cancer%20Fact%20Sheet%20Jan%202010.pdf

They are being very aggressive with the cancer push AND It's Happening!

v
Title: Re: Could this be the holy grail ?
Post by: Matty the Damned on January 21, 2010, 09:14:54 am
Hey Veritas,

You're familiar with confirmation bias, yes?

MtD
Title: Re: Could this be the holy grail ?
Post by: veritas on January 21, 2010, 09:47:11 am

MTD,

I'm fully aware of the term ---- confirmation bias.

I'm simply reporting the progress of a new paradigm ----- anti-ps therapy ----- as it runs through it's stages of development.

Are you familiar with the moa of this new paradigm? How it doesn't attack the virus directly, but attaches to the virus uncloaking it's ability to hide from the immune system. This represents a unigue mechanism that has been embraced by the CHAVI group in developing a cure and a vaccine. Dr. Philip Thorpe's lab has been made a part of CHAVI. ( Dr. Thorpe is the inventor ).

Peer reviews have all been positive to date and the clinical trials thus far have shown top=line safety data as well as some efficacy in both cancer and viral applications.

Follow the research, I believe you will find it intriguing !

v

 
Title: Re: Could this be the holy grail ?
Post by: Matty the Damned on January 21, 2010, 10:02:30 am
Honey, It's great that you find all these links and stuff but has it ever occurred to you that you only see cures? Uncritically and without reservation?

This represents a unigue mechanism that has been embraced by the CHAVI group in developing a cure and a vaccine. Dr. Philip Thorpe's lab has been made a part of CHAVI. ( Dr. Thorpe is the inventor ).

Dr Thorpe eh? Given that you're familiar with confirmation bias, perhaps you're also familiar with this term: argumentum ad verecundiam.

MtD
Title: Re: Could this be the holy grail ?
Post by: veritas on January 21, 2010, 11:35:33 am

MTD,

I'm fully aware that the fact the potential therapy has been embraced by the CHAVI group , doesn't automatically mean it is going to be succesful. Dr. Thorpe's forte is in research with a bent for oncology.
He noticed that viruses  also display PS on their outer coat thus  sparking the anti-viral work. This mechcanism was picked up by the CHAVI group for study in the HIV arena.
This happens to be a branch of hiv research that I find intriguing ,since, as stated before, it attacks a non-mutatable portion of the virus.
Cure? possibly. Vaccine? hopefully. Guarantees? NONE.


a propinquus mens est amo a propinquus libri a congeries .

v
Title: Re: Could this be the holy grail ?
Post by: Matty the Damned on January 28, 2010, 06:19:04 am
Veritas,

Previously in this thread I spoke to you harshly. I regret that. I was high handed and arrogant, and I apologise to you. You're valued contributor here and you deserve better treatment than I handed you.

AIDSmeds has a well deserved reputation for excellence in HIV/AIDS education, treatment and testing information, not to mention community support.

It's a shame the Research forum lets AM down on that count.

I have to say my view of the AM Research forum is less charitable and I conflated my dim view of this sub-forum with your good faith contributions.

I hope you might allow Matty the Damned the benefit of the doubt on this occasion. :)

MtD
Title: Re: Could this be the holy grail ?
Post by: veritas on January 28, 2010, 02:23:42 pm
Matty,

I agree with respect to the reputation of Aidsmeds. The good work done here has helped many overcome the fears of being  afflicted with HIV as well as providing excellent information to discuss with their IDs. Many people read these forums looking for information on topics that can certainly be  difficult to live with. More often, than not, they find that information.

With respect to the Research Forum, I only agree to a certain extent. This forum is quite different from others in that, here, we are dealing with theoreticals and potentials.  Personal opinion doesn't mean much here unless it can be backed -up with appropriate reference. It takes a lot of searching and dot connecting to reach that goal and not everyone is willing or able to do the necessary research. However, what this forum does provide is proof that HIV is being researched by some of the greatest minds in medicine and this alone is enough to be hopeful. We're not  forgotten. Sure, I'd like to see more in-depth research on some topics as to who, what, where, when, why, whither and whatfor but, again, that can be difficult.
Let's not cut this forum short.

As for your remarks to me, I kinda like arrogant self confident guys. I think I'll check out Quantus flights to Perth (since I hear, Perth is similar to Newport, RI , a resort town I like to visit). Hope your not in Sydney.

v


Title: Re: Could this be the holy grail ?
Post by: veritas on January 28, 2010, 02:50:40 pm

The Keystone Symposia -- Look at who's talking on Monday, March 21. Is it CHAVI? Yep.

http://www.keystonesymposia.org/meetings/ViewMeetings.cfm?MeetingID=1051

It's Happening!

v
Title: Re: Could this be the holy grail ?
Post by: veritas on January 31, 2010, 01:32:35 pm

Progress with antibodies --- Bavituximab mentioned as a possible "Holy Grail" antibody.:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2800955/pdf/nihms89559.pdf



"Anti-virals remain a healthy market, with numerous small molecules and antibody based
therapeutics in development and the primary emphasis on HIV and hepatitis B and C [3]. This
is partly because of the need for treatments in these areas and the continuing effectivity of the
17 polyclonal human immunoglobulin preparations available in the US [4]. Major challenges
when designing antibody therapies against viruses include identification of potently
neutralizing epitopes which are conserved across serotypes and the potential for rapidly
evolving viruses to generate escape variants which are no longer inhibited by the antibody.
Combination therapies, either an antibody co-administered with a small molecule (i.e.,
ribavirin) or a combination of neutralizing antibodies binding distinct epitopes can address
these issues"

"The “holy grail” anti-viral antibody would be one which targets a generic aspect of viral
pathogenesis, an antibody that could be used to treat a wide range of viral infections without
the need to diagnose the specific virus responsible for infection or concern over development
of escape variants. One antibody with this potential has been reported in US patent
7,455,833, an anti-phospholipid antibody marketed as Bavituximab by Peregrine
Pharmaceuticals, Inc"

Should I sue them for using my  "by-line" --- LOL

It's Happening !!!!!

v
Title: Re: Could this be the holy grail ?
Post by: Rev. Moon on January 31, 2010, 02:32:50 pm

Should I sue them for using my  "by-line" --- LOL


I am vexed! How dare they :)
Title: Re: Could this be the holy grail ?
Post by: veritas on January 31, 2010, 04:21:08 pm
I am vexed! How dare they :)


Not to mention wretched, since I published first !

I think I'll settle for a complete round of second generation Bavi therapeutic.

That's it !

v
Title: Re: Could this be the holy grail ?
Post by: veritas on February 06, 2010, 06:51:34 am

CAVD reports interim progress reports on the:

Project: Broadly Reactive Neutralizing Antibodies: Novel Strategies for Vaccine Design


http://www.cavd.org/grantees/Pages/progressAbstracts_Haynes.aspx

It's Happening !

v
Title: Re: Could this be the holy grail ?
Post by: veritas on February 08, 2010, 06:45:36 pm







 More evidence showing that phosphilipids are a good selective target.




'There is a major ongoing research effort to identify oligonucleotide
and protein biomarkers of malignant disease.1 Phospholipid
biomarkers are less common; however, there is increasing evidence
that the membrane surfaces of certain cells and particles of
biomedical significance, such as apoptotic cells,2 activated cells,3
tumor vasculature,4 microvesicles,5 bacteria,6 and viruses,7 expose
unusually high levels of negatively charged phospholipids. Proteins
and antibodies that can selectively target these anionic membrane
surfaces and distinguish them from the near-neutral membrane
surfaces of normal human cells have promising potential as imaging
probes,8 drug delivery agents,9 and targeted molecular therapeutics.
10 Notable examples are the protein, Annexin V, which is under
clinical investigation as an imaging probe for dead/dying tissue,11
and the antibody, Bavituximab, which targets viruses and tumor


vasculature.12 It is often challenging to optimize the formulation
and pharmaceutical properties of proteins; thus, there is a need to
develop small molecule mimics of these proteins that exhibit the
same targeting capabilities'

http://pubs.acs.org/doi/pdf/10.1021/ja908467y?cookieSet=1

IT'S HAPPENING !


v
Title: Re: Could this be the holy grail ?
Post by: veritas on February 11, 2010, 10:29:33 am

Here is the latest news on cotara, a therapy for brain cancer. The take away for this therapy  can be found in this statement of the release:

"Additionally, the median survival time of the 28 patients was 38 weeks, a 58% increase over the historical median survival time of 24 weeks for GBM patients treated with standard-of-care therapy."

 http://ir.peregrineinc.com/releaseDetail.cfm?ReleaseID=444373

Now you might ask: what does this have to do with bavituximab? If cotara works that good alone, think of the possibilities ,if they combined cotara with bavituximab as a missle and payload therapy for Brain Cancer !! The results could be enhanced, imho. Not to mention all other types of cancers, many of which, hiv positive patients are afflicted. ( If you have been following this thread, the cancer indications have been reported here, also.)

Still no negative peer reviews that I could find. Anxiously waiting for anti-viral news.

It's Happening !

v
 









Title: Re: Could this be the holy grail ?
Post by: veritas on February 11, 2010, 12:46:46 pm

For those who aren't familiar with Glioblastoma Multiforme (GBM), see these stats from UCLA:

http://www.neurooncology.ucla.edu/Performance/GlioblastomaMultiforme.aspx

These stats will allow the reader to understand how remarkably cotara performed.


v
Title: Re: Could this be the holy grail ?
Post by: veritas on February 15, 2010, 06:09:00 am
A stronger more powerful antibody found, stronger than any others found to date ---- m9.

 " M9 was much more potent than scFv 17b, and more potent than or comparable to the best-characterized broadly neutralizing hmAbs IgG1 b12, 2G12, 2F5 and 4E10"

"These results suggest that m9 is a novel anti-HIV-1 candidate with potential therapeutic or prophylactic properties, and its epitope is a new target for drug or vaccine development".

https://www.landesbioscience.com/journals/mabs/article/11416

How about a Bavi missle with an m9 payload ?

It's Happening !!

v

ps: take a peak at the researchers co-authoring this paper ------ the first string of hiv research!
Title: Re: Could this be the holy grail ?
Post by: aferstilo on February 15, 2010, 08:03:00 am
Wow last post seems great, I Have great hope that something reall good will happen very soon for us!!
Title: Re: Could this be the holy grail ?
Post by: veritas on February 15, 2010, 01:20:26 pm

Background on m9 (technical):

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC108702/

Seems like m9 recognises a protein on cell surfaces, whereas bavi recognises a fat (ps). Perhaps , there are synergies with the two therapies to enhance therapeutic effect (missle and payload). Promising !

The science is certainly going forward.

It's Happening !

v
Title: Re: Could this be the holy grail ?
Post by: Inchlingblue on February 15, 2010, 01:31:29 pm
Nice find. What do they mean by an "engineered" antibody? I assume they mean it's man-made.
Title: Re: Could this be the holy grail ?
Post by: veritas on February 15, 2010, 02:01:50 pm

Inch,

Your right, m9 is man-made. This allows the antibody to be made in quantity at a reasonable price (hopefully), not only for therapeutic use but also possibly as a vaccine. A costly vaccine won't solve the third world aids problem as readily due to funding. Now the questions are: Will it be effective in humans? When will they start the trials? Is it safe?

Let's hope we catch a break !

v
Title: Re: Could this be the holy grail ?
Post by: veritas on February 15, 2010, 06:56:43 pm

Bavituximab call out ---------

"Bavituximab is a drug currently undergoing trials for treatment of hepatitis C and HIV. It destroys body cells that harbor the virus, so it does offer promise of curing latent infections such as herpes."

http://www.dispatch.com/live/content/life/stories/2010/02/15/2_DONO0215.ART_ART_02-15-10_D2_O3GI9RB.html?sid=101

It's Happening!

v
Title: Re: Could this be the holy grail ?
Post by: veritas on February 19, 2010, 09:21:38 am

Further evidence from CROI that anti-ps antibodies can neutralize hiv:

http://www.retroconference.org/2010/Abstracts/37104.htm

"Here, we demonstrate that anti-E2 antibodies neutralize HIV-1 and 2, as well as SIV by targeting Phospholipids within the retroviral lipid bilayer. In a comparable manner, these lipid structures are recognized by the broad HIV neutralizing antibodies (BNAb) 2F5, 4E10, and Z13e1. Therefore, we demonstrate for the first time that such lipid targeted BNAb can be elicited by a heterologous viral glycoprotein, outlining new promising HIV vaccination strategies."

It's Happening !

v
Title: Re: Could this be the holy grail ?
Post by: veritas on March 05, 2010, 06:16:10 am

Bill Gates, Anthony Fauci, Anti-ps and HIV ------ It's Happening!

http://www.peregrineinc.com/index.php?option=com_content&task=view&id=85&Itemid=151


v
Title: Re: Could this be the holy grail ?
Post by: veritas on March 07, 2010, 10:35:37 am

Will cd8 cells play a role in any vaccine against HIV? Do long term non-progressors use cd8s to control the virus? Duke gives us some insight:

http://jvi.asm.org/cgi/content/abstract/JVI.00138-10v1?maxtoshow=&hits=10&RESULTFORMAT=&fulltext=duke+research+2010&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT

IT's Happening!

v
Title: Re: Could this be the holy grail ?
Post by: veritas on March 11, 2010, 05:26:40 am

IAVI reports on: Lipids, Antibodies and Vaccine briefs along with research updates from CROI:

http://www.iavi.org/lists/iavipublications/attachments/409aee04-63a3-4f83-b432-3be08f7b4913/iavi_iavi_report_jan-feb_2010_eng.pdf

A long read, however, it's up to the minute research for those who are interested.

It's Happening !!

v
Title: Re: Could this be the holy grail ?
Post by: veritas on March 13, 2010, 05:11:19 am

Anti-ps and cancer ------- could a possible cancer vaccine be in the not too distant future?

http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=442fffe5-4c06-49dd-8502-558fd7965952&cKey=40051adb-f50a-47d5-a7b9-7e3fae7fed5b&mKey=%7b0591FA3B-AFEF-49D2-8E65-55F41EE8117E%7d

"These results have important implications for our understanding of the immunosuppressive effects of PS in cancer and could lead to the development of a novel whole cell cancer vaccine strategy in which PS-blocking is used to enhance immunogenicity."

It's Happening!



Title: Re: Could this be the holy grail ?
Post by: brazilianman on March 16, 2010, 08:37:58 am
 :'(veritas, I have followed with hope that study of anti-ps. but we need something more practical. peregrine not released the results yet. Why? bavituximab like to see on the shelves of pharmacies dealing with us positive, not in a room search for life. :'(
Title: Re: Could this be the holy grail ?
Post by: veritas on March 16, 2010, 10:11:34 am

braziliaman,

Nice to hear from you, you haven't been posting for awhile. Glad your back.

To answer your question, Baituximab is being pushed full steam ahead by Peregrine for cancer indications. It seems they are leaving the viral end to others like CHAVI (for HIV) and Dept of Defense for other viral indications. They are also applying for more patents concerning both indications since it seems their R&D (UTNW) keeps coming up with more efficient antibodies. If you would like to peruse the history of anti-ps in the form of patents right up- to the present, see this:

http://www.freepatentsonline.com/7678386.html

The company has stated that they will release the data on the HEPC/HIV study by this coming Sept. My gut feeling is that the results will be positive or they wouldn't be putting so much effort and funding into anti-ps research along with CHAVI and DOD who are also expending funds to research same. Again, this research is not on our timeline. So we wait. However, I still have not found one negative peer review with respect to this research which is pretty remarkable since the research goes back to the late 90s.

v

Title: Re: Could this be the holy grail ?
Post by: carpediem98 on March 17, 2010, 10:20:07 am
This is anecdotal rather than publicly reported, but a friend's mother is a mid-career HIV researcher, currently working on anti-PS therapies. She said that their success has been "astonishing, but with roadblocks." My friend eagerly suggested I try to get into the study as an anonymous patient (as it would be ethically questionable to knowingly recruit a family friend); the mother suggested I wait until the next phase, at which time they'll have fixed dosing and a full safety profile - and a location in NYC (the work is currently happening in NJ and, she says, at Penn).

When I tried to dig a little more, she sort of clammed up, but more in a "Please, can I not talk about work on my day off" sort of way than a "We're trying to keep this a secret" sort of way.
Title: Re: Could this be the holy grail ?
Post by: veritas on March 17, 2010, 10:46:20 am

carpe,

Interesting post. There is a lot more to this therapy than the obvious. One of the roadblocks is mounting the appropriate immune response (antibodies in sufficient quantities) to go after the virus once exposed to the immune system by anti-ps. That issue is only a matter of time. I'm not too worried about the safety issue with respect to the anti-ps mab since it has been injected into enough people (especially those with cancer) with no major adverse effects. By the way, the cancer results have been incredible to date. Wait till ASCO.
Some of those cancer patients were terminal.
I do understand her concern for the  safety issue. Most are concerned about the immune system attacking the body. However, this did not happen in the hepc trials or the cancer trials (quite the opposite). I believe their concern is with the newer, stronger (fully Human) mabs which hopefully will do the trick.

Stayed tuned ---- this is exciting stuff.

v
Title: Re: Could this be the holy grail ?
Post by: brazilianman on March 17, 2010, 12:56:53 pm
veritas,

hope bavituximab out of the petri dish to my veins and blood (lol) as soon as possible. I believe that one infusion per week is better than taking pills every day. I plan to bavituximab before happy hour.

bman
Title: Re: Could this be the holy grail ?
Post by: veritas on March 18, 2010, 05:16:44 am

bman,

Your quote: " I plan to bavituximab before happy hour."



I love it -------- bavituximab with a chaser !

v
Title: Re: Could this be the holy grail ?
Post by: carpediem98 on March 19, 2010, 07:56:44 pm
I still like my concept for the MAB/resveratrol weekly infusion complex - HIVEXITROL. :^)

Can I start whining now about the fact that in 2013 we have to have infusions of the weekly medicine instead of pill form?
Title: Re: Could this be the holy grail ?
Post by: veritas on March 26, 2010, 05:49:31 am


Anti-ps  reverses the inhibition of tumor immunity by the exposed PS on tumor cells. Vaccine potential for cancer! Abstract to be presented at AACR this year in April:

http://www.abstractsonline.com/Plan/ViewAbstract.aspx?sKey=442fffe5-4c06-49dd-8502-558fd7965952&cKey=40051adb-f50a-47d5-a7b9-7e3fae7fed5b&mKey=%7b0591FA3B-AFEF-49D2-8E65-55F41EE8117E%7d

v
Title: Re: Could this be the holy grail ?
Post by: veritas on March 29, 2010, 01:38:08 pm

Could this be why we haven't heard much about Bavi anti viral ?

https://researchfunding.duke.edu/detail.asp?OppID=5645

Interesting........

v
Title: Re: Could this be the holy grail ?
Post by: veritas on April 02, 2010, 05:37:25 am
Duke is breaking their silence on anti-ps therapy.

"“The beauty of this newly identified set of antibodies -- called polyreactive anti-phospholipid antibodies -- is that they are so potent against the type of virus that establishes infection during mucosal transmission,” says Anthony Moody, MD, a member of the Center for HIV/AIDS Vaccine Immunology (CHAVI) at Duke and lead author of the study appearing in the Journal of Experimental Medicine'

"Moody says the antibodies, PGN632, P1, IS4 and CL1, do not appear to have any pathogenic features, even though other members of the class do. Earlier studies by others have demonstrated that anti-phospholipid antibodies have anti-viral effects, but “what we have done in this paper is to show how they do that,” Moody says."

 
"While the findings still have to be tested clinically, they do suggest a new way the immune system might be manipulated to thwart HIV, said Barton Haynes, MD, director of CHAVI and the Duke Human Vaccine Institute and senior author of the study. “There are two parts of the immune system -- the innate and adaptive components -- and this study shows a vaccine that could elicit these polyreactive antibodies could recruit both components to fight HIV.”  

http://www.dukehealth.org/health_library/news/scientists_identify_how_a_novel_class_of_antibodies_inhibits_hiv_infection

Something tells me not only is it happening, it will be happening fairly soon !!! Bring on the clinical trials !!

v

PS: The study will be published in the "Journal of Medicine" on Apr.5.2010. The title of the study:"Scientists Identify How A Novel Class Of Antibodies Inhibits HIV Infection"








Title: Re: Could this be the holy grail ?
Post by: veritas on April 02, 2010, 02:16:38 pm

Duke has password protected the article and link. We will have to wait until April 5 for the study to be released.

I hope they don't push back the release date.

Why all this secrecy with respect to anti-ps anti-viral is beyond my understanding. I hope it isn't ego induced! Because  if anti-ps anti-viral didn't have any effect, it would have been dropped a long time ago. Let's see what CHAVI (Duke) does on Monday.

v
Title: Re: Could this be the holy grail ?
Post by: xman on April 02, 2010, 08:36:34 pm
Something tells me not only is it happening, it will be happening fairly soon !!! Bring on the clinical trials !!

If they haven't even start with clinical trials, then it has a long way to go until being ready for primetime.

I believed they had start with trials  ???
Title: Re: Could this be the holy grail ?
Post by: veritas on April 03, 2010, 06:01:45 am

Xman,

The clinical trials for HIV directly will be coming out of CHAVI. The mabs they will be using are a lot more powerful than the mab used in the co-infection trial with HEPC/HIV. This has all been explained earlier to you in this thread. It is working wonderfully in the early cancer trials (phase 2). No-one said it is going to be done quickly. However, a clinical trial with the more potent mabs would be welcome to verify the science in an HIV setting and give an indication as to the potency of the more powerful mabs in vivo.

v
Title: Re: Could this be the holy grail ?
Post by: veritas on April 05, 2010, 09:44:42 am


IT'S HAPPENING !!!!

http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=456463


"Barton Haynes, M.D., director of the Duke Human Vaccine Institute and senior author of the study commented, "These results indicate that targeting a host cell lipid such as PS as an anti-viral strategy is a promising concept of relevance to new therapeutic and possibly prophylactic innovations for HIV."

"This publication is the latest in a series of presentations and publications that supports the potential of PS as a target in HIV infection and provides new insights into the unique mechanisms of action of our PS-targeting antibodies," said Steven W. King, president and CEO of Peregrine. "While past studies have focused on the broad nature of the PS target, these new data reveal that some of these antibodies may also have highly specific effects."

Bring on the clinical trials !!!

v
Title: Re: Could this be the holy grail ?
Post by: veritas on April 05, 2010, 09:58:47 am


http://esciencenews.com/articles/2010/04/05/scientists.identify.how.a.novel.class.antibodies.inhibits.hiv.infection

The above is the article that was blocked by DUKE last week.

IT'S HAPPENING !!!!!

v
Title: Re: Could this be the holy grail ?
Post by: veritas on April 05, 2010, 04:27:30 pm

Here's the abstract from the above two posts:

http://jem.rupress.org/content/early/2010/04/02/jem.20091281.abstract


IT'S HAPPENING !!!

v
Title: Re: Could this be the holy grail ?
Post by: veritas on April 06, 2010, 05:34:20 am

Why is the above research so important?  A wonderful summary:

"In summary, these non-pathogenic PS-targeting antibodies owe their unprecedented success at inhibiting HIV infection** to a surprising indirect mechanism of action that induces the production of beta chemokines, molecules known to prevent HIV infection by occupying a receptor that HIV uses to enter cells. The specific chemokines responsible for the HIV inhibition are known as MIP-1-alpha and MIP-1-beta, also known as CCL3 and CCL4, respectively. The antibodies are orders of magnitude more potent at inhibiting HIV infection of cells than previously discovered and much-touted rare broadly neutralizing antibodies that target the exterior viral spike of HIV directly. Due to their extreme potency at low concentrations, if additional studies with these antibodies continue to show promise, they may eventually hold potential as active ingredients in preventative microbicides to block initial infection or as therapy for people already infected with the virus. The antibodies may also provide a clear goal for the design of vaccines to stimulate the rapid production of similar antibodies upon exposure to the virus, in hopes of conferring protective immunity to HIV infection"
jbm/blog

If these antibodies work as expected, at the minium we have a functional cure, if not an outright cure.

Could anti-ps be the Holy Grail ?  You decide!

IT'S HAPPENING !!!

v
Title: Re: Could this be the holy grail ?
Post by: xman on April 06, 2010, 01:55:02 pm
If these antibodies work as expected...

yeah that's the big question. your entusiasm is understandable but what worries me is the fact that we don't have a safety profile and we don't know if works. since fda requires human trials which we all know takes years we should be more caution about the possible outcomes of this approach. not to mention the financial assistance which is needed to end all the trials. when we are in phase 2 then i guess it's the moment to make some considerations. now it's too early. just my opinion.
Title: Re: Could this be the holy grail ?
Post by: veritas on April 09, 2010, 09:45:08 am

Xman,

You didn't disappoint with your answer.  I'm going to give you another hint concerning anti-ps: beta-chemokines. They _may_ be the key as to why anti-ps may work and others may not.

v
Title: Re: Could this be the holy grail ?
Post by: stargate12 on April 09, 2010, 11:08:33 am
yeah that's the big question. your entusiasm is understandable but what worries me is the fact that we don't have a safety profile and we don't know if works.

I understood that bavituximab is being tested for cancer  right now.... and therefore there is no safety  issue concerning.
Title: Re: Could this be the holy grail ?
Post by: veritas on April 09, 2010, 12:52:26 pm

Stargate12,

You are correct, however, in all fairness the mabs CHAVI have are more powerful than the 3g4 antibody being tested right now in the cancer study. The trials being done do show the viability of anti-ps.

For those who are interested, here is the full paper from my above posts (all 23 pages):

"In this paper, we define a mechanism of inhibition of HIV-1
infection of human PBMCs by human anti-phospholipid
antibodies"


http://www.peregrineinc.com/media/siteFiles/10-04-05_JEM_Moody_HIV_Purchased_Website.pdf

IT'S HAPPENING !!!!

v

Title: Re: Could this be the holy grail ?
Post by: mercuryman on April 09, 2010, 12:59:44 pm
Will bavituximab only work against R5 virus or will it also work against DUAL TROPIC (X4/R5) virus?
Title: Re: Could this be the holy grail ?
Post by: veritas on April 09, 2010, 01:14:23 pm

mercuryman,

YES !  It has been posted earlier in the thread.

v

Title: Re: Could this be the holy grail ?
Post by: xman on April 09, 2010, 01:43:27 pm
Xman,

You didn't disappoint with your answer.  I'm going to give you another hint concerning anti-ps: beta-chemokines. They _may_ be the key as to why anti-ps may work and others may not.

v

well you agree that we will not see this as a therapeutical option for many years, right?
Title: Re: Could this be the holy grail ?
Post by: veritas on April 09, 2010, 01:46:26 pm

Define "many"!

v
Title: Re: Could this be the holy grail ?
Post by: xman on April 09, 2010, 01:48:53 pm
10 years
Title: Re: Could this be the holy grail ?
Post by: veritas on April 09, 2010, 01:51:56 pm

 "LESS" than 10 years!

Title: Re: Could this be the holy grail ?
Post by: xman on April 09, 2010, 01:55:45 pm
I appreciate your optimism and attitute toward this approach but you know that human trials require on average 7/8 years for completition, maybe less if fast tracked. Look at the Virxsys candidate which is indeed fast tracked but requires years to definitely pass from one phase to another. Now they are planning for a phase 2b which will need another 2 years for being done.

I'm not skeptical about the MOA but about the necessary timeline to put this product in our hands (or better in our mouths)
Title: Re: Could this be the holy grail ?
Post by: veritas on April 09, 2010, 02:00:26 pm

Xman,

A drug can be released after phase 2 given the right circumstance.

v
Title: Re: Could this be the holy grail ?
Post by: veritas on April 11, 2010, 05:28:15 am
What makes the attached article concerning anti-ps and hiv intrigueing is where it is published --------- Genetherapy:

 http://www.genetherapy.me/peregrine-pharmaceuticals-reports-data-from-newly-published-research-reinforcing-potential-of-targeting-ps-in-hiv-infection/

'Because the PS target is host-derived rather than pathogen-derived, PS-targeting antibodies are expected to be less susceptible to the viral genomic mutations that lead to anti-viral drug resistance'.

Could that mean any retro- viral "genomic" mutation?  YUP !

It's Happening !!

v

ps: "PS-targeting antibodies have been shown to help clear infectious virus from the bloodstream and to induce antibody-dependent cellular cytotoxicity. "  Can you guess what that means?
Title: Re: Could this be the holy grail ?
Post by: stargate12 on April 12, 2010, 12:00:57 pm

ps: "PS-targeting antibodies have been shown to help clear infectious virus from the bloodstream and to induce antibody-dependent cellular cytotoxicity. "  Can you guess what that means?

Mhmmm... hiv eradication?...
Title: Re: Could this be the holy grail ?
Post by: veritas on April 12, 2010, 12:33:56 pm

stargate12,


  ADAPTIVE IMMUNITY !!!!!


v
Title: Re: Could this be the holy grail ?
Post by: veritas on April 12, 2010, 12:58:01 pm

Adaptive Immunity Explained


CD8+ T lymphocytes and cytotoxicity
Main article: Cytotoxic T cell
Cytotoxic T cells (also known as TC, killer T cell, or cytotoxic T-lymphocyte (CTL)) are a sub-group of T cells which induce the death of cells that are infected with viruses (and other pathogens), or are otherwise damaged or dysfunctional.[1]

 

Killer T cells—also called cytotoxic T lymphocytes or CTL-directly attack other cells carrying certain foreign or abnormal molecules on their surfaces[5].Naive cytotoxic T cells are activated when their T-cell receptor (TCR) strongly interacts with a peptide-bound MHC class I molecule. This affinity depends on the type and orientation of the antigen/MHC complex, and is what keeps the CTL and infected cell bound together.[1] Once activated, the CTL undergoes a process called clonal expansion in which it gains functionality, and divides rapidly, to produce an army of “armed”-effector cells. Activated CTL will then travel throughout the body in search of cells bearing that unique MHC Class I + peptide.

When exposed to these infected or dysfunctional somatic cells, effector CTL release perforin and granulysin: cytotoxins which form pores in the target cell's plasma membrane, allowing ions and water to flow into the infected cell, and causing it to burst or lyse.[1] CTL release granzyme, a serine protease that enters cells via pores to induce apoptosis (cell death). To limit extensive tissue damage during an infection, CTL activation is tightly controlled and generally requires a very strong MHC/antigen activation signal, or additional activation signals provided by "helper" T-cells (see below).[1]

Upon resolution of the infection, most of the effector cells will die and be cleared away by phagocytes, but a few of these cells will be retained as memory cells.[3] Upon a later encounter with the same antigen, these memory cells quickly differentiate into effector cells, dramatically shortening the time required to mount an effective response.


v
Title: Re: Could this be the holy grail ?
Post by: Inchlingblue on April 13, 2010, 07:41:18 pm
aidsmeds.com has an article about anti-ps:

http://www.aidsmeds.com/articles/hiv_bavituximab_phsophatidylserine_1667_18272.shtml
Title: Re: Could this be the holy grail ?
Post by: veritas on April 14, 2010, 06:33:41 am

Inch,

Thanks for posting that link. The article is based on the paper published in the 'Journal of Experimental Medicine' posted above.

At the risk of sounding too optimistic, my gut tells me we might have something wonderful here. (The cancer indications are screaming! )

My guess is we could possibly have a therapeutic vaccine in the not too distant future or at least a damn good therapeutic.

It's Happening Inch !

v
Title: Re: Could this be the holy grail ?
Post by: Pepino2 on April 14, 2010, 02:13:06 pm
Peregrine Pharma released two news releases in the past two weeks as follows;

Peregrine Pharmaceuticals Reports Data from Newly Published Research Reinforcing Potential of Targeting PS in HIV Infection
Article in Journal of Experimental Medicine Shows that PS-Targeting Antibodies Can Block

One of the Ways the AIDS Virus Gains Entry into Blood Cells
http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=456463 (http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=456463)

Peregrine Announces Data From Four Clinical Studies Will Be Presented at 2010 ASCO Annual Meeting
Will Include Data From Bavituximab Breast and Non-Small Cell Lung Cancer Phase II Studies and Cotara Brain Cancer Study
http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=458641 (http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=458641)

Stock up to $3.99 from $3.54 prior to releases.

Title: Re: Could this be the holy grail ?
Post by: J220 on April 14, 2010, 05:37:58 pm
Good news just keep coming from Peregrine!

Let it happen!!
Title: Re: Could this be the holy grail ?
Post by: veritas on April 15, 2010, 05:17:52 am

Pepino, J220,

Thanks for the links. The news coming out of Perigrine is indeed hopeful as J220 points out.

 However, let me reiterate that as far as the stock is concerned, there is still a lot of risk and no-one should use money they desperately need to buy this stock.  Sure the rewards could be substantial, but other influences come into play besides top notch science when dealing with bio-techs. They are high risk/reward by their nature.

My main focus is on the science. I don't want to see the science, with the potential to make a real impact on our struggle, get mired in financial potential.

If you want to invest, that is your personal decision ------ this thread makes no claims to that affect.

v

Title: Re: Could this be the holy grail ?
Post by: veritas on April 15, 2010, 09:37:44 am

Anti-ps attacks breast cancer  ------ amazingly:

http://finance.yahoo.com/news/New-Study-Shows-Combining-iw-935939111.html?x=0&.v=1

It's Happening !

v
Title: Re: Could this be the holy grail ?
Post by: J220 on April 15, 2010, 11:09:47 am
Pepino, J220,

Thanks for the links. The news coming out of Perigrine is indeed hopeful as J220 points out.

 However, let me reiterate that as far as the stock is concerned, there is still a lot of risk and no-one should use money they desperately need to buy this stock.  Sure the rewards could be substantial, but other influences come into play besides top notch science when dealing with bio-techs. They are high risk/reward by their nature.

My main focus is on the science. I don't want to see the science, with the potential to make a real impact on our struggle, get mired in financial potential.

If you want to invest, that is your personal decision ------ this thread makes no claims to that affect.

v



Good disclaimer...on second thought I'll withdraw that part of my earlier post and maybe start a new thread specifically on that subject on another section....My apologies for the derail.
Title: Re: Could this be the holy grail ?
Post by: veritas on April 19, 2010, 09:26:35 am


"New Preclinical Breast Cancer Study Shows Peregrine's PS-Targeting Antibodies Can Reverse Tumor-Induced Immune Suppression"

http://www.marketwire.com/press-release/New-Preclinical-Breast-Cancer-Study-Shows-Peregrines-PS-Targeting-Antibodies-Can-Reverse-NASDAQ-PPHM-1149634.htm

Begs the question: How can HIV immune suppression be reversed?

v
Title: Re: Could this be the holy grail ?
Post by: veritas on April 21, 2010, 08:49:40 am

Anti-ps has cancer in its' crosshair:

http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=461809

It's happening !

v
Title: Re: Could this be the holy grail ?
Post by: J220 on April 21, 2010, 05:43:42 pm
Amazing...regardless of what it does on the HIV front if it can target tumors and become a potent arsenal against cancer then this will be revolutionary.
Title: Re: Could this be the holy grail ?
Post by: veritas on May 11, 2010, 10:35:09 am


'sCD4-17b neutralizes HIV-1 with high potency and great breadth against genetically diverse primary isolates. It is equivalently active against virus particles generated from different producer cell types (cell line versus PBMC). These results support the continued investigation of various modalities by which sCD4-17b can be employed against HIV infection.'

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2843639/?tool=pubmed

v
Title: Re: Could this be the holy grail ?
Post by: veritas on May 11, 2010, 01:44:47 pm

Treatment Action Group ( TAG ) following anti-ps therapy:

http://www.treatmentactiongroup.org/basicsciblog.aspx?id=3664&blogid=88

"Interestingly, there have also been reports recently that anti-phospholipid antibodies can directly inhibit HIV. The postulated mechanism for this activity is the binding of antibodies to cellular phospholipids that HIV incorporates into its viral membrane when budding out of infected cells. At CROI in San Francisco earlier this year, Heidi Reil showed that some antibodies against the E2 protein of a virus called GBV-C bind phospholipids and can also inhibit HIV (in the TZM-bl assay). Reil’s talk is available among the CROI webcasts (the last presentation in the Thursday abstract session on HIV vaccines). "

It's Happening!


v
Title: Re: Could this be the holy grail ?
Post by: veritas on May 17, 2010, 01:31:01 pm

A complete, concise overview of Peregrine Pharmaceuticals, including up to date research with anti-ps mabs with respect to all anti-viral and anti-cancer data. The report is extensive (80 pages), however, very readable. Anyone interested in anti-ps therapy, this report is a very informative read:

http://www.crystalra.com/pdf/PPHM_EIO_05-17-2010.pdf

From reading this report, more anti-ps clinical trials will be initiated by Peregrines collaborators. I hope HIV therapeutic is among them soon.

However, it's happening.

v
ps: it will take a few moments to load depending on your computer speed.
Title: Re: Could this be the holy grail ?
Post by: veritas on May 24, 2010, 09:45:43 am


CHAVI's latest update:

https://chavi.org/wysiwyg/downloads/CHAVI_Newsletter_3_3.pdf

Check out the anti-ps antibody study on page 5--------- adaptive immunity, is it happening?

YUP !

v
Title: Re: Could this be the holy grail ?
Post by: veritas on May 27, 2010, 09:52:44 am

In a phase 2 clinical trial for ADVANCED breast cancer, the anti-ps antibody, Bavituximab, 74% of patients show tumour response and progression-free survival. 9% had a complete response----- the tumor was gone! (advanced breast cancer is one of the more difficult to treat).

http://finance.yahoo.com/news/Phase-II-Advanced-Breast-iw-1732419195.html?x=0&.v=1

Is it happening in cancer?  YOU BETCHA!!!

v
Title: Re: Could this be the holy grail ?
Post by: veritas on June 11, 2010, 04:58:05 pm

The latest fact sheet on Bavituximab-- anti-viral :

http://www.peregrineinc.com/images/stories/media/siteFiles/Bavituximab_Antiviral_June_2010.pdf


It's Happening (and" possibly" in the not too distant future) !


v
Title: Re: Could this be the holy grail ?
Post by: J220 on June 12, 2010, 12:21:01 am
I really have high hopes for this MOA. And I particularly like the fact that there is already an ongoing Phase 1 for HIV. For all we know they could determine even at this early stage that this does work and anti-PS therapy does clear the infection. Imagine if as we speak they are analysing data and can't find any trace of HIV in the patients treated with this? Can't wait to hear more results.
Title: Re: Could this be the holy grail ?
Post by: veritas on June 12, 2010, 11:52:33 am

An interesting article on monoclonal antibodies (bavi-like):

http://www.sciencedaily.com/releases/2010/06/100611124651.htm

Short term therapy for long term treatment of chronic viral infections.

Can you say adaptive immunity?

v
Title: Re: Could this be the holy grail ?
Post by: ElZorro on June 12, 2010, 03:59:02 pm
V

Do you have any information as to how long the trial of people who are coinfected with HIV/HCV will run (the one that is ongoing)?
Title: Re: Could this be the holy grail ?
Post by: veritas on June 13, 2010, 05:26:57 am

Zorro,

This combination trial has been going on for some time now. I believe data should be released this Sept. The mab (bavituximab- 3g4 antibody), which is being used in that trial, is not the strongest anti-ps antibody. CHAVI is in the process of pre-clinicals with much stronger mabs. The results of the on-going trial with 3g4 will give us a good look into anti-ps in the setting of hiv. CHAVI is the group going for the homerun.

v
Title: Re: Could this be the holy grail ?
Post by: veritas on June 13, 2010, 06:33:01 pm

"Breast Cancer News" -- "New drug may be next huge breakthrough in breast cancer:

http://www.thebreastcancersite.com/clickToGive/bcs/article/New-drug-may-be-next-huge-breast-cancer-breakthrough337

Can you guess what it is?

Yup --- It's Happening!

v
Title: Re: Could this be the holy grail ?
Post by: xman on June 13, 2010, 10:41:25 pm
What worries me is that 3 years passed and Bavituximab is still in an ongoing phase I trial for HCV/HIV. It's quite long for a phase I. They should at least know something on the safety profile and efficacy but to date nothing was published about this study. Obviously HIV is not the main target and on top of the agenda. Instead more is done on the cancer part. If a miracle happened we would know it by now. I'm not convinced.
Title: Re: Could this be the holy grail ?
Post by: J220 on June 14, 2010, 08:23:35 pm
What worries me is that 3 years passed and Bavituximab is still in an ongoing phase I trial for HCV/HIV. It's quite long for a phase I. They should at least know something on the safety profile and efficacy but to date nothing was published about this study. Obviously HIV is not the main target and on top of the agenda. Instead more is done on the cancer part. If a miracle happened we would know it by now. I'm not convinced.

Well it could be the other way around, for all we now. Maybe this therapy worked better than expected, say this managed to clear the infection from the patients. I think they would want to be 100% sure of their results before they made an annoucement. Perhaps they are waiting more time than normal in order to be completely sure of their resuts. Just a hypothesis on my part, but as equally possible than saying it's not working. We simply don't know either way. So until they share data, I'm keeping my hopes up.
Title: Re: Could this be the holy grail ?
Post by: veritas on June 15, 2010, 04:45:06 am

xman,

If you read this thread with comprehension, you would know that it does work to some degree against viral infection. I personally just want to see some efficacy from the co-infection trial. The 3g4 antibody they are using is not the strongest anti-ps mab as I have stated here a number of times. I will say again CHAVI will be the entity to push HIV therapy with anti-ps. By the way, 3g4 showed efficacy against hepc in earlier trials, there is no reson to think it won't show the same against hiv. Geez, have a little foresight and stop carrying that dark cloud around with you.

j220,

Remember, everyone needs their pound of flesh, if you get my meaning. Researchers are jealous gods!

v
Title: Re: Could this be the holy grail ?
Post by: xman on June 15, 2010, 08:26:22 am
xman,

If you read this thread with comprehension, you would know that it does work to some degree against viral infection. I personally just want to see some efficacy from the co-infection trial. The 3g4 antibody they are using is not the strongest anti-ps mab as I have stated here a number of times. I will say again CHAVI will be the entity to push HIV therapy with anti-ps. By the way, 3g4 showed efficacy against hepc in earlier trials, there is no reson to think it won't show the same against hiv. Geez, have a little foresight and stop carrying that dark cloud around with you.

Please allow some criticism. CHAVI is still in a preclinical phase and we still don't know when they will start on human trials. I'm only skeptical because I see progress on the cancer front and not on HIV. They're not pushing on HIV research and the current phase I is moving very slowly. If you have an answer to the slow progress then please tell us.
Title: Re: Could this be the holy grail ?
Post by: veritas on June 15, 2010, 09:30:36 am

xman,

I have given you and others the reason why progress in the specific hiv arena is moving so slowly. Why do you think that a company would prolong a phase1 trial that costs a lot of money to continue for 3 years if they haven't seen some type of progress? Do you think that there could be outside influences causing the delay? Why would the DOD want to study anti-ps in their bioterrorist program? Why did CHAVI make Dr. Thorpe's lab part of their crusade for a vaccine and cure? Why is all this money being spent to research anti-ps? If you can't back-up your staements with appropriate research and links then I won't accept criticism  from you. I'll tell you again, this research is not on our timelines and unfortunately,we will just have to wait. Let me tell you, if I find a research paper that shows this research
not to be viable, I'll post it. Until you do the same, I find your whining annoying. Who knows, you just might be surprised sooner than you think!

v





 to be
Title: Re: Could this be the holy grail ?
Post by: xman on June 15, 2010, 09:52:28 am
veritas,

the clinical development is plenty of abandoned components which at the end stage didn't reach the expected results. One of them is the last Bevirimat, a promising maturation inhibitor, which you welcomed with the same enthusiasm as for the anti-ps. This just to present you some facts and failures in HIV research. My criticism is legitimate because we know that a development can be stopped in any phase. As long as I have not convincing data in my hands I'll remain skeptic.
Title: Re: Could this be the holy grail ?
Post by: veritas on June 15, 2010, 10:19:16 am

xman,

I welcome any research that has the possibility to put a dent in this horrible disease. Some will work out others won't. I take issue with your comparison of my enthusiasm with Bevirimat with that of anti-ps! I didn't write a 12 page thread on bevirimat! Bevirimat wasn't tested for many indications like anti-ps. Anti-ps has been tested in humans for many types of cancers and hepc and now hiv. Your arguement is flawed as usual. What I don't understand is why you keep reading this thread if you feel so skeptical about it. Why don't you just wait until the final results are in to make your comments? This thread is not required reading. I think you just like to complain. Others are interested in the research progress step by step. It's for those interested parties that I continue this thread. Don't worry, if I find that anti-ps falls short of my expctations, I'll close this thread and look for next possible breakthrough. That day isn't here yet!

v
Title: Re: Could this be the holy grail ?
Post by: colossus on June 15, 2010, 10:38:07 am
xman,

you are making ad hominem.
I don't think anyone is here to see your negative behavior.

veritas,

thank you very much for your great and informing posts. You always find the last minute updates. This is the only thread I regularly follow in this site.
Title: Re: Could this be the holy grail ?
Post by: xman on June 15, 2010, 10:41:57 am
xman,
 
I don't think anyone is here to see your negative behavior.



I think mine is a more realistic behavior. Someone is able to see the difference. If you like dreaming with open eyes than continue so if this will let you feel better.
Title: Re: Could this be the holy grail ?
Post by: xman on June 15, 2010, 10:58:21 am
xman,

What I don't understand is why you keep reading this thread if you feel so skeptical about it. Why don't you just wait until the final results are in to make your comments? This thread is not required reading. I think you just like to complain. Others are interested in the research progress step by step. It's for those interested parties that I continue this thread. Don't worry, if I find that anti-ps falls short of my expctations, I'll close this thread and look for next possible breakthrough. That day isn't here yet!

v

What surprises me is the fact that you're promoting an approach without having any, or very poor data, about it's efficacy in relation only of HIV. You're relying on your gut as you claimed many times. Sure the MOA seems promising but dude, we are still in phase I and only God knows what could happen to this and other ones during the slow and long lasting clinical process and development.

I also take seriously in consideration that no expert to date, neither here or on other sites, are crying for enthusiasm about this and other approaches. They are all very tempered. Only you with your 'it is happening' slogan, not to mention that nothing concrete is really happening since 2006 on the anti ps and HIV front, are pushing optimism over something that still has a far and hard way to go before reaching primetime. Sure you have your audience but many perhaps put too much hope in something that will not reach our mouths until the next decade. This is my opinion. You can share or discuss it. But you need to understand that not everybody feels so much enthusiams about something and, to avoid confusion, I'm posting that here.  

Title: Re: Could this be the holy grail ?
Post by: colossus on June 15, 2010, 11:27:24 am
lets look at the big picture

1981 -> hiv is identified.
1996 -> first effective drugs (ART) had been found
2007 -> first cured person from disease (Berlin patient)
???? -> hiv becomes history.

so I think something is happening.

PS: xman, go away nobody likes you! (by Eric Cartman).
Title: Re: Could this be the holy grail ?
Post by: Boze on June 15, 2010, 11:36:32 am
What surprises me is the fact that you're promoting an approach without having any, or very poor data, about it's efficacy in relation only of HIV. You're relying on your gut as you claimed many times. Sure the MOA seems promising but dude, we are still in phase I and only God knows what could happen to this and other ones during the slow and long lasting clinical process and development.

I also take seriously in consideration that no expert to date, neither here or on other sites, are crying for enthusiasm about this and other approaches. They are all very tempered. Only you with your 'it is happening' slogan, not to mention that nothing concrete is really happening since 2006 on the anti ps and HIV front, are pushing optimism over something that still has a far and hard way to go before reaching primetime. Sure you have your audience but many perhaps put too much hope in something that will not reach our mouths until the next decade. This is my opinion. You can share or discuss it. But you need to understand that not everybody feels so much enthusiams about something and, to avoid confusion, I'm posting that here.  



What's stopping you from abandoning this thread? You've made it clear that you don't share veritas' enthusiasm for the said program. You also don't actually seem to have any real knowledge about it - only speculation about why it's going slow, etc.
I think a healthy enthusiasm is a good thing - helps to keep us going, knowing that research on many fronts is being done toward the disease. Nobody here is cancelling their HAART prescription because of "unwarranted hope" that you are skeptical about.
Hence I don't see the point of continued negativity in light of the absence of facts at your disposal.
Title: Re: Could this be the holy grail ?
Post by: xman on June 15, 2010, 11:52:27 am
You also don't actually seem to have any real knowledge about it - only speculation about why it's going slow, etc.
 
Hence I don't see the point of continued negativity in light of the absence of facts at your disposal.

Oh yes but you have knowledge, right? The absence of facts? Please read carefully and provide facts that tell the opposite. What lacks here is a healthy and reality based confrontation. I know that the reality can hurt but I sincerely prefer having hope in something more concrete. Maybe I'm trying to ease your pain when all your hopes in this one might break down all at once.
Title: Re: Could this be the holy grail ?
Post by: Boze on June 15, 2010, 03:55:38 pm
Oh yes but you have knowledge, right? The absence of facts? Please read carefully and provide facts that tell the opposite. What lacks here is a healthy and reality based confrontation. I know that the reality can hurt but I sincerely prefer having hope in something more concrete. Maybe I'm trying to ease your pain when all your hopes in this one might break down all at once.

I am not putting too much hope into any given strategy - and to be honest haven't really followed this one closely. I am encouraged by the plethora of different approaches that are being tried. With the amount of technical wherewithal put to bear, a result should come about one way or another.

As far as this drug - I see no downside about hope. Hope is a potent tool in our arsenal - why be a party pooper?
Title: Re: Could this be the holy grail ?
Post by: ElZorro on June 15, 2010, 07:28:57 pm
Quote
Why do you think that a company would prolong a phase1 trial that costs a lot of money to continue for 3 years if they haven't seen some type of progress? Do you think that there could be outside influences causing the delay? Why would the DOD want to study anti-ps in their bioterrorist program? Why did CHAVI make Dr. Thorpe's lab part of their crusade for a vaccine and cure? Why is all this money being spent to research anti-ps?

V

I'll admit to being new to this, excited about the information that you post, but also, curious as to what you think the answers to these questions are. I can see that this thread has been here for a couple years, but when I google for current results, there doesn't seem to be a lot of tangible information for the lay person.

I feel in my bones that the researchers are getting extremely close to a homerun, but can't help but wonder if, as a "newbie", I'm too naive and hopeful.
Title: Re: Could this be the holy grail ?
Post by: veritas on June 16, 2010, 04:54:12 am

Zorro,

The simple answer to all those questions is that the MOA (mechanism of action) of anti-ps therapy has intrigued the top researchers in the world to the point that they are willing to spend a lot of money for the study of this novel therapeutic paradigm. The dept of defense feels the same way. You will not find the answers with a simple google search. You have to dig in to journals and follow research of those drs. doing the research. This is not easy to do and takes a lot of tiime. The aforementioned is why many shy away from this forum. The evidence is there -- you have to read the thread in full which includes scientific papers that are sometimes difficult to understand. This is xman's problem-- he doesn't understand the research and clinical trial procedure and he is making statements akin to a scared, anxiety ridden little boy, who probably is having a hard time coping with his infection. One can't stamp their foot and get what they want--- life doesn't work that way. If one makes statements they had better be able to back up what they say with links and research. Without proof, opinions are meaningless. All the evidence that I have enumerated in this thread have been backed up by research and links. However, one has to read the thread to get the full meaning of my posts. Also, of course, one has to understand what is being said. The research on this therapy is not complete, there is no time-line set up yet for clinical trials by CHAVI. So we must wait for the research to develop. Every step forward means "It's Happening".

v
Title: Re: Could this be the holy grail ?
Post by: ElZorro on June 16, 2010, 07:18:16 pm
Every step forward means "It's Happening".

from your lips to God's ears  ;) 

I feel like with all that seems to be happening, "they" [the research community] ought to bump into a cure by accident if nothing else  8)
Title: Re: Could this be the holy grail ?
Post by: xman on June 16, 2010, 09:10:30 pm
This is xman's problem-- he doesn't understand the research and clinical trial procedure and he is making statements akin to a scared, anxiety ridden little boy, who probably is having a hard time coping with his infection. One can't stamp their foot and get what they want--- life doesn't work that way. If one makes statements they had better be able to back up what they say with links and research. Without proof, opinions are meaningless. All the evidence that I have enumerated in this thread have been backed up by research and links.

veritas,

are you scientist or a MD? I guess not. You as a self esteemed dabbler in science are simply posting articles from other sites and organizations, adding your comments and thoughts based on nothing than what you feel. Please post your personal references and credentials instead of putting yourself a on a higher scale. And please don't missunderstand me. I'm not a doctor or researcher too but many facts are telling that, althought the application of anti-ps is very promising, it is still too early to comment and to emphasize. This for the common sense of putting a limit to an exceeded enthusiasm, which is clearly the case here.

Title: Re: Could this be the holy grail ?
Post by: xman on June 16, 2010, 09:30:37 pm
And for not seeming a pessimist or an anxiety ridden little boy who is whining and hopeless, I say that I would be very glad to congratulate veritas for his thoughts and gut feelings if those should turn in something real. It's not for demonstrating any superiority in comparison with veritas or anybody else. On the contrary I try to keep a rational and tempered attitude on this and other studies and researches as many doctors and experts recommend. I don't like to put too much hope in something that as far as we actually know, hasn't demostrate nothing really worth to celebrate so far.
Title: Re: Could this be the holy grail ?
Post by: veritas on June 17, 2010, 05:45:07 am

xman,

You do no research, you do-not understand the references, you contribute nothing to the thread other than to cause conflict ----- all in all pretty sad.  Your a distraction to every thread you post in. I don't want you posting in this thread any further.

Moderators please review. I believe he was told earlier in the thread not to post here unless he had something constructive to say. His criticism is based on no research other than his feelings and he is disrupting those members who are interested in the subject. He repeats the same questions answered many times and makes statements which he evidently can't defend. If he doesn't share the interest in this research that others seem to do, there is really no reason for him to post here. Please rule.

v

Title: Re: Could this be the holy grail ?
Post by: Ann on June 17, 2010, 10:31:43 am
xman,

Back in September 2009 you were politely asked by (then moderator) Jan (anniebc) to stay out of this thread if you had nothing constructive to add. Yet here you are, back again, giving Veritas a hard time. If V and other members feel excited about this research, then so be it. Who are you to tell them that they shouldn't be?

If you disagree with people's opinions of this research, then simply stay out of the thread. As a poster above noted, this thread is not required reading.

Leit/Xman

If you don't agree with anything Veritas has to say or have nothing constructive to say then stay away from his thread..ridiculing other posters is not allowed, and childish behaviour is just, well...childish.

So unless you have somthing to say that has anything to do with the subject being discussed here then stay out of this discussion.

Jan


I'm not going to be quite as polite as Jan was - STAY OUT OF THIS THREAD! I'm tired of getting complaints about your antics here. Please consider yourself warned!

Ann
Title: Re: Could this be the holy grail ?
Post by: xman on June 17, 2010, 09:18:43 pm
xman,

Back in September 2009 you were politely asked by (then moderator) Jan (anniebc) to stay out of this thread if you had nothing constructive to add. Yet here you are, back again, giving Veritas a hard time. If V and other members feel excited about this research, then so be it. Who are you to tell them that they shouldn't be?

If you disagree with people's opinions of this research, then simply stay out of the thread. As a poster above noted, this thread is not required reading.

I'm not going to be quite as polite as Jan was - STAY OUT OF THIS THREAD! I'm tired of getting complaints about your antics here. Please consider yourself warned!

Ann

if you read carefully what jan posted it was about ridiculizing other members and about not posting things directly related to the thread title.

I'm simply exposing my disagreement on some positions here and I'm not offending anyone. I guess you understand this. I didn't broke any rule. If this isn't permitted than this forum is not a civil and democratic place for discussion. Perhaps you don't like uncomfortable comments on the views of some members here.
Also this forum in my opinion is becoming unserious and an important moderator left a similar comment some time ago in another thread about this issue. I'll quote it below.

Sadly, our research forum has become one big circle jerk of (badly) self-taught research "experts" for their list of future cures.

This was my last post here.
Title: Re: Could this be the holy grail ?
Post by: Rev. Moon on June 17, 2010, 09:33:55 pm

This was my last post here.

Good riddance!

Children, back to your sandbox.
Title: Re: Could this be the holy grail ?
Post by: Ann on June 18, 2010, 11:18:26 am
xman,

I've replied to your PM rather than hijack this thread with an explanation of why and how you're offending people.

Ann
Title: Re: Could this be the holy grail ?
Post by: freewillie99 on June 18, 2010, 07:10:56 pm
an important moderator left a similar comment some time ago in another thread about this issue. I'll quote it below.

That quote, rather than sounding like it came from an "important moderator" (whatever that means), sounds much more like the grousing of a bitter old gueen.

This was my last post here.

Tragic.
Title: Re: Could this be the holy grail ?
Post by: veritas on June 27, 2010, 05:15:47 am
Bio-defense Vaccines and Therapies -- June 14-17,2010.

http://www.infocastinc.com/downloads_pdf/biodef10_symp.pdf

"Phosphatidylserine-Targeting Broad Spectrum Antibodies for
the Treatment of Hemorrhagic Fever Virus Infections
Peregrine Pharmaceuticals Inc. and it academic collaborators are
developing broad spectrum anti-viral agents. These anti-viral
monoclonal antibodies target anionic phospholipids such as
phosphatidylserine (PS) which become exposed on the surface of
virus-infected cells and egressed virions. The antibodies exert their
anti-viral effect via clearance of circulating virus and destruction
of virus-infected cells by antibody-dependent cell-mediated
cytotoxicity. We present data supporting the use of PS-targeting
antibodies against members of three major hemorrhagic fever virus
families including Pichinde virus and Junin virus (Arenaviridae),
Punta Toro virus (a model for Rift Valley fever virus,
Bunyaviridae family) and yellow fever virus (Flaviviridae).'
Melina Soares, Ph.D., Assistant Professor, University of Texas
Southwestern Medical Center at Dallas

HIV exposes ps also, now the question is: what is holding up clinical trials?

It's Happening!


v




Title: Re: Could this be the holy grail ?
Post by: Inchlingblue on June 27, 2010, 10:52:50 am

HIV exposes ps also, now the question is: what is holding up clinical trials?

It's Happening!


I guess if this were approved by the FDA for other viruses, it could then be used "off label" for HIV?
Title: Re: Could this be the holy grail ?
Post by: georgep77 on June 27, 2010, 10:28:24 pm
I guess if this were approved by the FDA for other viruses, it could then be used "off label" for HIV?
Smart move Inch .....    :P
Title: Re: Could this be the holy grail ?
Post by: veritas on June 28, 2010, 04:53:33 am
I guess if this were approved by the FDA for other viruses, it could then be used "off label" for HIV?

I don't see any reason why not.

v
Title: Re: Could this be the holy grail ?
Post by: stargate12 on July 07, 2010, 12:23:11 pm
 Peregrine's stock price was $2.15 then and $1.75 now. A 18.6% drop.

One of the most basic rules of investing is to never try and catch a falling knife. Very low percentage chance of success. Never try to catch a falling knife - ever.

What is the explanation of this drop ?
Title: Re: Could this be the holy grail ?
Post by: veritas on July 08, 2010, 04:37:00 am

stargate12,

This thread is NOT a stock blog. If an investor cannot figure out why a stock is moving in a certain way, they shouldn't be in the stock market.  I said here before, you invest at your own risk.

Please, start your own thread, if you want to discuss the stock market. This thread is dedicated to anti-ps science only.

v
Title: Re: Could this be the holy grail ?
Post by: veritas on July 14, 2010, 09:37:05 am

new phase II B trial for Non-small cell lung cancer (one of the most difficult cancers to treat) to commence:

http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=487983

Bavi has difficult cancers in the crosshairs!

Now when are we going to hear more from CHAVI? That's the question.

v
Title: Re: Could this be the holy grail ?
Post by: veritas on September 07, 2010, 09:49:38 am

The patent that  I have been waiting to see has been granted  excerpts:

"In both cases, the compositions, methods and uses inhibit one or more steps or stages necessary for a productive or ongoing viral infection, including inhibiting viral entry. Preferably, the compositions, methods and uses inhibit viral replication and/or spread, such as inhibiting one or more steps of viral transcription, translation, assembly, packaging and/or egress within or from an infected host cell, such as a mammalian or human cell. The invention therefore preferably limits or substantially confines viral infections to initially infected cells and cell populations, thus substantially inhibiting or preventing the subsequent or ongoing infection of additional host cells or tissues."

"As the invention inhibits one or more steps or stages necessary for productive or ongoing infection common to all viruses, the anti-viral methods and uses of the invention are suitable for treating all viruses, both enveloped and non-enveloped viruses, including those that infect plants, animals, vertebrates, mammals and human patients. The invention is suitable for treating all viruses that infect vertebrates, as listed herein in Table H, particularly humans, and particularly viruses that are pathogenic in animals and humans. The viral infections and associated and resultant diseases that can be treated by the invention include those viruses and diseases set forth in Table J, as exemplified by treating CMV, RSV, arenavirus and HIV infections, and the diseases hepatitis, influenza, pneumonia, Lassa fever and AIDS. "

If you read this patent (it's long), remember 3g4 is in clinical trials for  combo hepc/hiv.

http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=7,790,159.PN.&OS=PN/7,790,159

It's Happening!


v
Title: Re: Could this be the holy grail ?
Post by: Inchlingblue on September 07, 2010, 11:00:06 am
Wow, that's exciting.

Is this patent for several monoclonal antibodies?
Title: Re: Could this be the holy grail ?
Post by: veritas on September 07, 2010, 02:07:27 pm

Inch,

The patent focuses on two antibodies (3g4 and 9d2) both are anti-ps antibodies with the 3g4 antibody seemingly the preferred. Remember that these antibodies are the "guidance system that directs the payload". Both of these antibodies can be armed with almost any nrti, nnrti and pi to do the job. The fact that the payload is target- directed, substantially, lowers the risk of AEs.

Of course these antibodies can be directed to cancers also (ie: KS, lung etc) with a different payload. Currently in phase 2 clinical trials for cancer with the 3g4 antibody.

v
Title: Re: Could this be the holy grail ?
Post by: veritas on September 10, 2010, 09:14:05 am


Steve King, CEO of Peregrine Pharm., answers a question concerning Bavi and hiv therapeutic, hinting at the data they are seeing in the hep/c/ Hiv trial:

"Any thought on possibly moving forward with a drug cocktail in HIV as well? Obviously what the data shows but –

Steve King

Yeah, I think we'll let the data drive that discussion. But I think absolutely. Again Bavi is really designed if you will for combination therapy with direct antivirals in the infectious disease area."

v
Title: Re: Could this be the holy grail ?
Post by: Inchlingblue on September 11, 2010, 01:48:53 am

Steve King, CEO of Peregrine Pharm., answers a question concerning Bavi and hiv therapeutic, hinting at the data they are seeing in the hep/c/ Hiv trial:

"Any thought on possibly moving forward with a drug cocktail in HIV as well? Obviously what the data shows but –

Steve King

Yeah, I think we'll let the data drive that discussion. But I think absolutely. Again Bavi is really designed if you will for combination therapy with direct antivirals in the infectious disease area."

v


So he is saying that it's designed to be used alongside ARVs?
Title: Re: Could this be the holy grail ?
Post by: veritas on September 11, 2010, 09:54:58 am

Inch,

Bavi is the guided missle, ARVs are the payload (perhaps antibodies also, as being studied by CHAVI). The ARVs can be attached to bavi (see posts above) to enhance the effectiveness of the therapy and diminish AEs. I know the patent is a long read, but there is a lot of neat information contained within the patent that explains the MOA.

v
Title: Re: Could this be the holy grail ?
Post by: veritas on October 08, 2010, 09:18:52 am
Defense threat initiative conference in Nov:

 http://cbdstconf2010.sainc.com
Agenda: http://cbdstconf2010.sainc.com/conference_agenda/tentative_agenda.aspx
11-16-10 6-8pm, Track: Host-Directed Therapeutics & Immunomodulation
Poster #T02-003, “Targeting of Anionic Phospholipids Exposed on Infected Cells & Virions: Potential Broad-Spectrum Antiviral Therapy”
Kara Corbin-Lickfett, Peregrine Pharmaceuticals

v
Title: Re: Could this be the holy grail ?
Post by: veritas on October 08, 2010, 06:00:04 pm

This power point presentation was showcased at the International AIDS vaccine conference in Atlanta during sept. Dr. Gary Nabel of CHAVI was the presenter. The same antibodies used for a preventative vaccine can also be used as a therapeutic. The pathway is becoming focused. Is there light at the end of the tunnel? It seems so.

http://nationalpress.org/images/uploads/programs/ATLj2j_Nabel.ppt

v
Title: Re: Could this be the holy grail ?
Post by: ElZorro on October 08, 2010, 10:47:03 pm
Pretty slides, V, but what do they mean?  :-\
Title: Re: Could this be the holy grail ?
Post by: tednlou2 on October 09, 2010, 02:36:11 am
The following video was suggested to me by YouTube--obviously because I've watched other HIV videos there.  I know, of course, this has all been discussed here--A3G and Vif.  Has this video been shown?  Very interesting.  Sometimes it is easier for me to understand things when produced on video than reading research papers.

http://www.youtube.com/watch?v=GmQ0dg9djak&feature=grec_index
Title: Re: Could this be the holy grail ?
Post by: veritas on October 09, 2010, 05:42:37 am
Pretty slides, V, but what do they mean?  :-\

Bottom line,  the first draft (rather exciting) Blueprint of a preventative/therapeutic vaccine.

 

v
Title: Re: Could this be the holy grail ?
Post by: ElZorro on October 09, 2010, 12:26:48 pm
Great video...thanks for posting, TnL
Title: Re: Could this be the holy grail ?
Post by: veritas on November 06, 2010, 04:14:57 pm

CHAVI expects human clinical trial using newly designed vaccine by 2012:

Consortium Assembled to Design Human Trials of Mosaic HIV Vaccine
Michelle Gailiun
Duke University Medical Center michelle.gailiun@duke.edu
October 18, 2010
An international team of scientists will design and implement the first human trial of a mosaic HIV vaccine candidate, a novel strategy that attempts to counter one of the most daunting challenges in HIV vaccine design: the virus's extensive genetic diversity.
Traditional HIV vaccines are designed to stimulate the body's immune system to recognize naturally occurring stretches of specific amino acids in the virus's proteins. In contrast, mosaic vaccines are composed of many sets of synthetic, computer-generated sequences of proteins that can prompt the immune system to respond to a wide variety of circulating HIV strains.
Such vaccines have already been studied in animals and have shown some success in enhancing the breadth of immune responses. Now, Barton Haynes, MD, director of the Duke Human Vaccine Institute and the Center for HIV/AIDS Vaccine Immunology (CHAVI), says a newly formed research coalition has begun designing an early phase safety trial to assess mosaic vaccines in humans. The trial will test the mosaic concept and could possibly lead to the next generation of HIV vaccine candidates.
Haynes, who will lead the consortium, says the group will use the NYVAC vaccinia vector (derived from the vaccine to protect against smallpox) and DNA that contain a new set of artificial computer-designed HIV genes in a phase I clinical trial that will be supported by the Bill & Melinda Gates Foundation and the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.
Haynes says the consortium hopes to launch human trials by late 2012.
The consortium includes many of the world's leading researchers and organizations committed to finding an effective vaccine to protect against HIV infection, including the Foundation for the National Institutes of Health, the Fred Hutchinson Cancer Research Center and its NIH-funded HIV Vaccine Trials Network, the IPPOX Foundation in Switzerland, Beth Israel Deaconess Medical Center, Los Alamos National Laboratory, the NIH/NIAID Vaccine Research Center, Duke University and its Center of HIV/AIDS Vaccine Immunology, the Bill & Melinda Gates Foundation and the Division of AIDS of the National Institute of Allergy and Infectious Diseases.
Bette Korber, a senior scientist at Los Alamos National Laboratory and leader of the team that developed the mosaic genes, noted "HIV's diversity is vast, and the mosaic gene design represents a novel vaccine design to directly tackle HIV diversity in human clinical trials. Based on computational models, mosaic vaccines were predicted to perform better than natural HIV genes; experimental studies in animals that directly compared mosaic to natural vaccines supported that prediction. We are excited to test this concept in humans."
"Each member of this consortium is also a member of the Global HIV Vaccine Enterprise, and this collaboration is truly a global effort to make progress on HIV vaccine development," said Haynes.
The NYVAC vaccine is being provided by Sanofi-Pasteur, which is a collaborator in the study. The clinical development of NYVAC HIV vaccines has to date been conducted in Europe primarily through the EuroVacc Program.

v
Title: Re: Could this be the holy grail ?
Post by: ElZorro on November 06, 2010, 05:37:57 pm
V

Is this therapeutic, preventative, or both? Also, any information on how long the trial will last after it starts?
Title: Re: Could this be the holy grail ?
Post by: veritas on November 10, 2010, 09:52:45 am
Zorro,

The only info I have is as posted above.

I don't think the final protocols for the trial have been developed yet. The good news is that the vaccine is a mosaic candidate that will attempt to attack the virus's extensive genetic diversity and hopefully respond to a wide variety of the (circulating ) viral strains. This approach has never been tried before. We'll have to see what develops.

They are being somewhat obtuse.

v
Title: Re: Could this be the holy grail ?
Post by: veritas on November 17, 2010, 04:14:23 pm

Why have we not heard more about Bavi's potential in HIV? Why hasn't CHAVI been more forthcoming?
(hint:$$$$$)

Connect the dots.

Perhaps some answers:

http://finance.yahoo.com/news/Peregrines-Bavituximab-iw-604776925.html?x=0&.v=1

http://files.shareholder.com/downloads/PPHM/1069248692x0x420006/ffdc0f81-aa97-4a16-97d2-3ab72e7c2d74/cbdst2010.pdf

http://www.forbes.com/2010/10/21/bioterror-vaccines-manufacturing-technology-breakthroughs-biodefense.html

CHAVI is working with PGN 635 on hiv (part of the mosaic vaccine).

v
Title: Re: Could this be the holy grail ?
Post by: veritas on January 10, 2011, 10:35:31 am

BAVI tackles HEPC in a phase two trial. Therapy to last for TWELVE weeks in conjunction with ribavirin:

http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=542635

Results, hopefully, will be published in June. Could Hepc have a kinder and gentler therapy in the making?
What about other retro-viruses?

"Researchers have found that PS is exposed on the outer membrane of cells infected with HCV, HIV, influenza, herpes viruses, hemorrhagic fever viruses, respiratory syncytial virus, measles as well as other viruses. A growing body of scientific publications, including Nature Medicine and The Journal of Experimental Medicine, has highlighted data on the role of PS and Peregrine's PS-targeting therapies in infectious diseases."



Time will tell.

v
Title: Re: Could this be the holy grail ?
Post by: stargate12 on January 10, 2011, 12:16:56 pm
In prior HCV clinical trials, bavituximab administered as monotherapy  also showed promising on therapy antiviral activity of up to 1.5 log viral load reduction. With limited resources Peregrine must really feel Bavi has a good shot at besting interferon's role in HCV treatment.
Fantastic.


Title: Re: Could this be the holy grail ?
Post by: veritas on January 14, 2011, 05:45:55 am

http://ebdgroup.com/partneringnews/2011/01/five-companies-armed-to-fight-the-war-on-infections-disease/


"Bavituximab is being developed by Peregrine Pharmaceuticals for use in both infectious diseases and oncology. This is an anti-phosphatidylserine-targeted monoclonal antibody. As Steven King, CEO, explained, “Phosphatidylserine is tightly bound to dead and dying cells and is one of the best tumor markers we’ve found.”  The immune system down-regulates in its presence, effectively allowing cancer and infectious diseases to slip past the immune system undetected. By targeting phosphatidylserine, “Bavituximab has the potential to be a broad spectrum agent against every virus we’ve looked at,” he concluded"

Could this be why the US govt is looking so closely at Bavi?  What is CHAVI doing with anti-ps and why did they make Dr. Thorpe's lab part of their group? I wonder how bavi faired in the hepc/hiv trial?

Time will tell, but it seems to be HAPPENING!

v
Title: Re: Could this be the holy grail ?
Post by: veritas on January 18, 2011, 05:18:28 pm

Look who's interested in Bavituximab:

http://www.google.com/patents?q=bavituximab&lr=&sa=N&start=0

These are the one's we can see.

Who else?

v
Title: Re: Could this be the holy grail ?
Post by: geobee on January 31, 2011, 11:55:56 am
News from Peregrine today -- here's the headline...

Peregrine Completes Patient Enrollment in Phase Ib HCV/HIV Coinfection Trial
Clinical Data From Targeted Antibody Bavituximab Expected in 2Q11

http://www.marketwire.com/press-release/Peregrine-Completes-Patient-Enrollment-in-Phase-Ib-HCV-HIV-Coinfection-Trial-NASDAQ-PPHM-1387496.htm

...and here's the text (except for the "About Peregrine" part...)

TUSTIN, CA--(Marketwire - January 31, 2011) - Peregrine Pharmaceuticals, Inc. (NASDAQ: PPHM), a clinical-stage biopharmaceutical company developing first-in-class monoclonal antibodies for the treatment of cancer and viral infections, today announced the completion of enrollment in the company's Phase Ib dose escalation safety study of bavituximab in patients coinfected with chronic hepatitis C virus (HCV) and HIV. Previously this month, Peregrine initiated a randomized Phase II HCV trial to evaluate 12 weeks of therapy with bavituximab, a phosphatidylserine (PS)-targeting monoclonal antibody with immune-modulating potential, in combination with the antiviral drug ribavirin versus standard of care, pegylated interferon alpha 2a and ribavirin.

"Completion of enrollment in our third Phase I HCV trial is an important milestone for our bavituximab antiviral program, and sets the stage for reporting clinical data at a medical conference in the second quarter of this year while we begin to evaluate combination treatment with the antiviral agent ribavirin in a recently initiated study," said Steven W. King, president and chief executive officer of Peregrine. "Though standard treatment for chronic HCV may soon evolve with the introduction of new targeted antiviral drug candidates, immune stimulation with interferon remains a critical component of therapy. Preclinical data support the potential combination of bavituximab and ribavirin and we look forward to seeing how this combination initially compares to standard interferon and ribavirin treatment for 12 weeks in our Phase II study for patients infected with HCV."

In prior HCV clinical trials, bavituximab administered as monotherapy in single and multiple doses demonstrated a positive safety profile with no dose-limiting toxicities or serious adverse events. Bavituximab as a monotherapy also showed promising on therapy antiviral activity of up to 1.5 log viral load reduction.

Bavituximab may address a fundamental "immune evasion" mechanism exploited by many infectious pathogens. A growing body of published data from researchers worldwide shows that bavituximab's PS target, exposed on the surface of cells infected by viruses and protozoan parasites, suppresses the immune system's ability to fight disease. PS-targeting antibodies such as bavituximab bind to PS and block the immunosuppressive signals created by the target, thereby allowing the immune system to mount a robust immune response against the pathogen.

About the Phase Ib HCV Trial
Peregrine's open-label, dose escalation safety study is designed to assess the safety and of bavituximab in up to 24 patients chronically infected with HCV and HIV. Patient cohorts received ascending dose levels of bavituximab weekly for up to 8 weeks. Primary endpoints include safety and pharmacokinetics, and secondary endpoints will measure HCV and HIV RNA by PCR. For further information about Peregrine's HCV trials, please visit www.peregrinetrials.com or http://www.clinicaltrials.gov/ct2/results?term=bavituximab.

About HCV
According to the U.S. Centers for Disease Control and Prevention, an estimated 3.2 million individuals in the United States have chronic hepatitis C virus (HCV) infection. Chronic HCV infection is a serious disease that can result in long-term health problems, including liver damage, liver failure, liver cancer, or death. It is the leading cause of cirrhosis and liver cancer and the most common reason for liver transplant in the United States. Approximately 8,000 to 10,000 people die every year from HCV-related liver disease.

About Bavituximab's Antiviral Approach
Bavituximab is the first in a new class of patented antibody therapeutics that target and bind to phosphatidylserine (PS), a specific phospholipid component of cell membranes. Bavituximab helps reactivate and direct the body's immune system to destroy infected cells and virus particles that exhibit this specific phospholipid on their surface. Since their target is host-derived rather than pathogen-derived, PS-targeting antibodies have the potential for broad-spectrum antiviral activity and are also expected to be much less susceptible to the viral mutations that often lead to drug resistance.

Researchers have found that PS is exposed on the outer membrane of cells infected with HCV, HIV, influenza, herpes viruses, hemorrhagic fever viruses, respiratory syncytial virus, measles as well as other viruses. A growing body of scientific publications, including Nature Medicine and The Journal of Experimental Medicine, has highlighted data on the role of PS and Peregrine's PS-targeting therapies in infectious diseases.


Title: Re: Could this be the holy grail ?
Post by: veritas on February 04, 2011, 06:00:37 am

geobee,

Thanks for posting the update.

It seems that quite a few people want a piece of Bavi. Look at this petition for herpes:


http://www.petition2congress.com/3986/view_all/

http://www.herpes-coldsores.com/messageforum/showthread.php?31113-Peregrine-Bavituximab-HSV&mode=linear

The question still remains " What is holding up the advance in infectious disease?".

DOD has been testing BAVI for a variety of infectious diseases for awhile now.

If it wasn't showing results, they would have dropped it like the plague!

Also, it's exciting to see all the potential cures being studied.  Who will reach the finish line first?

Actually, who cares, as long as the cure comes soon!

It's Happening !!

v








Title: Re: Could this be the holy grail ?
Post by: veritas on March 31, 2011, 06:23:09 am
CHAVI readies "mosaic" vaccine:

http://www.lanl.gov/news/releases/consortium_to_design_human_trials_of_mosaic_hiv_vaccine_nr.html

Is anti-ps a part of this mosaic?  If you have been reading this thread, you would know the answer.

It's Happening !!

v
Title: Re: Could this be the holy grail ?
Post by: veritas on April 01, 2011, 05:16:03 am


https://www.fbo.gov/index?s=opportunity&mode=form&id=df2901a24f7a771758a20995fb1e814f&tab=core&_cview=1
Title: Re: Could this be the holy grail ?
Post by: veritas on May 06, 2011, 05:20:00 am

CHAVI reports -- Executive Summary- April 2011:

https://chavi.org/wysiwyg/downloads/CHAVI_Y06_Executive_Summary.pdf

v
Title: Re: Could this be the holy grail ?
Post by: georgep77 on March 17, 2012, 01:52:38 am
So what's new with this WANNABE anti HIV compound ??

   I guess it's going to be ready in 20 years lol
Title: Re: Could this be the holy grail ?
Post by: sensual1973 on March 17, 2012, 01:29:52 pm
well its the donkey and the carrot,but hope is better than no hope.
Title: Re: Could this be the holy grail ?
Post by: hoosier69 on March 18, 2012, 05:34:23 pm
And what happened to veritas who always kept this thread updated?
Title: Re: Could this be the holy grail ?
Post by: ichigo_kun on March 18, 2012, 05:42:24 pm
i hope he's good, or
maybe theres no update yet
Title: Re: Could this be the holy grail ?
Post by: simpleguy on March 29, 2012, 04:29:58 pm
The pipeline (http://www.peregrineinc.com/pipeline/overview.html) at Peregrine does not mention hiv, and their antiviral (http://www.peregrineinc.com/pipeline/cot.html) research is about hep. c and sadly not about hiv. Maybe they'll revive research on fighting hiv with bavituximab later?