Could this be the holy grail ?

[veritas]

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

[xman]

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?

[veritas]

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

[veritas]

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

[brazilianman]

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... -

[xman]

brazilianman,

your link doesn't work

i guess that is old news. there are no updates on the peregrine homepage.

[brazilianman]

sorry
http://www.drugs.com/clinical_trials/positive-results-peregrine-pharmaceuticals-bavituximab-phase-l-hcv-trial-presented-aasld-meeting-2568.html

[brazilianman]

BAVITUXIMAB HCV

http://www.natap.org/2007/AASLD/AASLD_74.htm

[veritas]

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.

[brazilianman]

veritas
very good bavituximab monotherapy. 2 aplication reduction > 75% RNA VHC.

[xman]

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.

[veritas]

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

[brazilianman]

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.

[veritas]

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

[brazilianman]

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?

[veritas]

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

[brazilianman]

veritas

this is wonderful

I love anti-ps

[veritas]

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

[brazilianman]

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
 

[brazilianman]

nature journal

inside hiv1

http://www.nature.com/nature/journal/v460/n7256/

[Inchlingblue]

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

[elf]

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 )

[brazilianman]

verita

http://www.nature.com/nature/supplements/collections/hivaids/

[veritas]

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

[veritas]

Exposed ps on infected cells:

http://www.newscientist.com/data/images/archive/2720/27200101.jpg


v

[Inchlingblue]

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.

[xman]

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!

[brazilianman]

veritas

 news from nature

 focus hiv research

http://www.nature.com/nm/index.html

[Inchlingblue]

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.

 

[brazilianman]

they do not say to nothing of the Dr. Haynes in the focus hiv and nor in the supplemen.
nothing of anti-ps .

[veritas]

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

[veritas]

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

[xman]

the first link is only for registered members. could you post a summary of it?

[brazilianman]

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.

[veritas]

It's those lipids and mabs again - this time with cholesterol:

http://www.jlr.org/cgi/rapidpdf/jlr.M000372v1.pdf

It's happening!

v

[veritas]

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

[veritas]

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

[Inchlingblue]

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

[veritas]

Exposed ps on tumors:

http://www.benthamdirect.org/pages/content.php?CPD/2009/00000015/00000023/0008B.SGM

v

[xman]

Great. Any news reguarding HIV?

[veritas]

"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

[veritas]

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

[veritas]

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

[brazilianman]

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.

[sam66]

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

[veritas]

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

[sam66]

thanks  veritas,

                 now i know whats going on,

[veritas]

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

[veritas]

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

[xman]

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.