This will definitely take a lot of time to find drug/vacccine that can block this PD-1 and Tim-3 express without any harmful affect(autoimmuse) but this thoery sound promising.
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forget about auto immune problems--- we all have those now with hiv in us and with the meds in us, did you ever wake up all creaky and your joints kind of stiffer than normal and making sounds in morning that is because the meds are auto immune damaging i think and such
30 years ago the idea was that science had discovered monoclonal antibodies and when one was designed for every specific disease and every specific condition most all diseases would be cured, of course what has happened in last 30 years is the RISE of corp. finance and the take over of the world by corp. capitalism and finance at the COST of research and what is new and best, and toxic drugs are much more money makers for the mfg and for wall street. finally now we have a fully human monoclonal antibody for pd-1 this exists today, the idea 30 years ago when the idea of monoclonal antibodies was thought us was , and you gotta look up all these terms in wikipedia
that they would not have ANY side effects what so ever because they were fully human genetically engineered to attack specific diseases.
lets put it this way, if the mouse version and the rat version and the chimp version which is all fully genetically engineered for each of those species does not do any harm and the animal is thriving in the cage without any arthritis
should we not be ready to use on those 15 humans in USA who are dying EACH DAY from hiv perhaps half cannot be saved because the damage to the body is too great the damage to the immune system is too great from last 25 years or 20 years or 15 years
but isnt there compassionate use?? why are we not picketing in front of the one office in the world that has this
anti pd-1 fully human anti body???????????????????
do we have to wait to each of us slowly gets damaged from the assortment of meds , one after another that will / may eventually fail or develop resistance????
is this not worth a try????
there seems to be a critical mass of research and there needs to be a meeting of dr.s and researchers for compassionate use to save those who over next 5 years will die
i think that monoclonal antibodies would have been a billion times bigger if the "FINANCE sector" which is just a giant thieving machine to take money from everyone in the world would not have grown up around science,
it could be just as cheap to produce fully human monoclonal antibodies as toxic drugs if BY LAW they were demanded!!!!!
economies of scale and all that... http://en.wikipedia.org/wiki/Monoclonal_antibodies
Monoclonal antibodies (mAb or moAb) are monospecific antibodies that are identical because they are produced by one type of immune cell that are all clones of a single parent cell. Given (almost) any substance, it is possible to create monoclonal antibodies that specifically bind to that substance; they can then serve to detect or purify that substance. This has become an important tool in biochemistry, molecular biology and medicine. When used as medications, the generic name ends in -mab (see "Nomenclature of monoclonal antibodies").
leit:
"bimazek":
- nodoby knows HIV-disease pathogenesis for certain - the most recent hypothesis attributes HIV-disease progression to chronic immune activation and inflammation - in this perspective, PD-1 could even be a body defence mechanism in front of an invincible enemy (HIV) - even blocking PD-1, and so unleashing the immune system, it couldn't win the war against HIV, because it isn't able to recognize, and consequently destroy, the reservoirs.
On this point, you may read Guido Silvestri's talk at the last IAC (page 54, in particular).
On the other hand, I totally agree with you on unacceptable time between discoveries and trials: They have only been hindering virus replication for 12 years, while the facts prove that it's not enough (HIV-disease has only become longer and clinically different, but not less serious).
bimazek:
this is the only company in world that i know of that has patent for this anti-PD-1 and anti-CD70 antibody and it has been shown to be seemingly safe in humans for cancer treatment,
do we need to start activism and call this company and ask for immediate compassionate use trails to start for those failing all classes of meds based on the recent monkey successes outlined above
i think we can make it win win, can someone call them up and say we want to do protests in front of thier headquarters in NEW JERSEY and can we try to set up a win win situation where they can announce on TV cameras that they commit to immediate compassionate use trails to start for those failing all classes of meds based on the recent monkey successes outlined above for HIV poz guys and gals failing all meds
perhaps thiere are some poz guys who they treated who also had the cancer that this is in approval for
the reason they might want to do cancer first is because market is bigger
what is possible here
do we need to take to streets, call tv stations, set up meetings with thier CEO or senior people
can someone please call them, and get a time line
if we do not activate activism it may string out longer
were not anti bodies suppose to be LOW or NO side effects treatments for disease??? are we all not tired enough of all these toxic meds that have huge side effects (see side effects and lipo and mental entire sections to this forum for example)
can someone who knows the science and can evaluate this better see if this is a promising path that should have activism going on??
can we make it win win where we are asking for thier meds on TV and they agree to accelerate testing for compassionate use and start asap esp. for those who have the same cancer that this anti pd1 treats
for example....
we need to demand immediate trials of this for poz guys who have prostate cancer and or who have melanoma cancer and who are poz RIGHT
can someone call them and get some info
can someone in new jersey organize a meeting or a protest??
Medarex, Inc. (Nasdaq: MEDX) announced that the following clinical and preclinical abstracts for ipilimumab in melanoma, prostate cancer and other cancers, as well as for anti-PD-1 and anti-CD70 antibody candidates for cancer treatment, are expected to be the subject of presentations at the Annual Meeting of the American Society of Clinical Oncology, being held May 30-June 3, 2008 in Chicago:
Survival, Response, Safety and Biomarker Data of Ipilimumab in Melanoma
-- "Antitumor response and new lesions in advanced melanoma patients on ipilimumab treatment" (Abstract #3020, Developmental Therapeutics: Immunotherapy Session) -- Poster presentation and discussion from 2:00 p.m. to 6:00 p.m. local time on Friday, May 30, 2008.
-- "Long-term survival of patients with advanced melanoma who received ipilimumab administered at 10mg/kg every 3 weeks for 4 doses (induction dosing)" (Abstract #3018, Developmental Therapeutics: Immunotherapy Session) - Poster presentation and discussion from 2:00 p.m. to 6:00 p.m. local time on Friday, May 30, 2008.
-- "Potential immune biomarkers of gastrointestinal toxicities and efficacy in patients with advanced melanoma treated with ipilimumab with or without prophylactic budesonide" (Abstract #3022, Developmental Therapeutics: Immunotherapy Session) -- Poster presentation and discussion from 2:00 p.m. to 6:00 p.m. local time on Friday, May 30, 2008.
-- "Novel efficacy criteria for antitumor activity to immunotherapy using the example of ipilimumab, an anti-CTLA-4 monoclonal antibody" (Abstract #3008, Developmental Therapeutics: Immunotherapy Session) -- Oral presentation beginning at 4:30 p.m. local time one Saturday, May 31, 2008.
-- "Effect of prior treatment status on the efficacy and safety of ipilimumab monotherapy in treatment-naive and previously treated patients with advanced melanoma" (Abstract #9055, Melanoma Session) -- Poster presentation from 2:00 p.m. to 6:00 p.m. local time on Saturday, May 31, 2008.
-- "An analysis of the effectiveness of specific guidelines for the management of ipilimumab-mediated diarrhea/colitis: prevention of gastrointestinal perforation and/or colectomy" (Abstract #9063, Melanoma Session) - Poster presentation from 2:00 p.m. to 6:00 p.m. local time on Saturday, May 31, 2008.
-- "Model-based evaluation of ipilimumab dosage regimen in patients with advanced melanoma" (Abstract #9073, Melanoma Session) -- Poster presentation from 2:00 p.m. to 6:00 p.m. local time on Saturday, May 31, 2008.
-- "Safety and efficacy of ipilimumab with or without prophylactic budesonide in treatment-naive and previously treated patients with advanced melanoma" (Abstract #9010, Melanoma Session) -- Oral presentation beginning at 10:15 a.m. local time on Sunday, June 1, 2008.
-- "Efficacy and safety of ipilimumab induction and maintenance dosing in patients with advanced melanoma who progressed on one or more prior therapies" (Abstract #9021, Melanoma Session) -- Poster presentation and discussion from 2:00 p.m. to 6:00 p.m. local time on Sunday, June 1, 2008.
-- "Disease control and long-term survival in chemotherapy-naive patients with advanced melanoma treated with ipilimumab (MDX-010) with or without dacarbazine" (Abstract #9022, Melanoma Session) -- Poster presentation and discussion from 2:00 p.m. to 6:00 p.m. local time on Sunday, June 1, 2008.
-- "Dose effect of ipilimumab in patients with advanced melanoma: results from a phase 2, randomized, dose-ranging study" (Abstract #9025, Melanoma Session) -- Poster presentation and discussion from 2:00 p.m. to 6:00 p.m. local time on Sunday, June 1, 2008.
-- "Prolonged survival in objective responders to ipilimumab therapy" (Abstract #20004) -- Publication only.
Response and Safety Data of Ipilimumab in Prostate
-- "Phase 1 trial of ipilimumab (IPI) alone and in combination with radiotherapy (XRT) in patients with metastatic castration resistant prostate cancer (mCRPC)" (Abstract #5004, New Targeted Strategies for Patients with Prostate Cancer Session) -- Oral presentation beginning at 11:30 a.m. local time on Monday, June 2, 2008.
-- "Expanded phase 1 combination trial of GVAX immunotherapy for prostate cancer and ipilimumab in patients with metastatic hormone-refractory prostate cancer (mHRPC)" (Abstract #5146, Genitourinary Cancer Session) -- Poster presentation from 8:00 a.m. to 12:00 p.m. local time on Saturday, May 31, 2008.
Clinical and Preclinical Data of Additional Immunotherapy and Antibody-Drug Conjugate Programs
-- "Safety and activity of MDX-1106 (ONO-4538), an anti-PD-1 monoclonal antibody, in patients with selected refractory or relapse malignancies" (Abstract #3006, Developmental Therapeutics: Immunotherapy Session) -- Oral presentation beginning at 4:00 p.m. local time on Saturday, May 31, 2008.
-- "Antitumor activity of anti-CTLA-4 monoclonal antibody (mAb) in combination with ixabepilone in preclinical tumor models" (Abstract #3048, Developmental Therapeutics: Immunotherapy Session) -- Poster presentation from 2:00 p.m. to 6:00 p.m. local time on Sunday, June 1, 2008.
-- "Effect of a fully human anti-CD70 antibody on apoptosis and dephosphorylation of MAPK proteins in chronic lymphocytic leukemia" (Abstract #3073, Developmental Therapeutics: Immunotherapy Session) -- Poster presentation from 2:00 p.m. to 6:00 p.m. local time on Sunday, June 1, 2008.
More information about the ASCO Annual Meeting may be found at http://www.asco.org.
About Medarex
Medarex is a biopharmaceutical company focused on the discovery, development and potential commercialization of fully human antibody-based therapeutics to treat life-threatening and debilitating diseases, including cancer, inflammation, autoimmune disorders and infectious diseases. Medarex applies its UltiMAb(R) technology and product development and clinical manufacturing experience to generate, support and potentially commercialize a broad range of fully human antibody product candidates for itself and its partners. More than 40 of these therapeutic product candidates derived from Medarex technology are in human clinical testing or have had INDs submitted for such trials, with seven of the most advanced product candidates currently in Phase 3 clinical trials or the subject of regulatory applications for marketing authorization. Medarex is committed to building value by developing a diverse pipeline of antibody products to address the world's unmet healthcare needs. For more information about Medarex, visit its website at http://www.medarex.com.
Safety and activity of MDX-1106 (ONO-4538), an anti-PD-1 ... Safety and activity of MDX-1106 (ONO-4538), an anti-PD-1 monoclonal antibody, in patients with selected refractory or relapsed malignancies. ... www.asco.org/ASCO/Abstracts+&+Virtual+Meeting/Abstracts?&vmview=abst_detail_view&confID=55&abstractID.
2008 (May 20 suppl; abstr 3006) Author(s): J. R. Brahmer, S. Topalian, I. Wollner, J. D. Powderly, J. Picus, C. Drake, J. Covino, A. Korman, D. Pardoll, I. Lowy Abstract: Background: Programmed death-1 (PD-1), an inhibitory receptor expressed on activated T cells, may suppress antitumor immunity. Objectives of this first in human phase I trial of MDX-1106 (ONO-4538), a fully human IgG4 anti-PD-1 blocking antibody, are to evaluate safety and maximum tolerated dose (MTD). Other objectives include evaluation of pharmacokinetics (PK) and immunological effects. Methods: Patients (pts) had treatment refractory metastatic non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), colon cancer (CC), melanoma (MEL), or prostate cancer (HRPC), and no history of autoimmune disease. Sequential cohorts of 6 pts received a single IV dose of MDX-1106 at 0.3, 1, 3, or 10 mg/kg. Disease status was evaluated at wk 8 by RECIST criteria. Pts with SD or lesional responses could receive additional MDX-1106 at wks 12 and 16, at the original dose. Results: 24 pts, 6 at each dose level (9 CC, 5 NSCLC, 6 MEL, 4 HRPC), were enrolled through 11/07. 23 pts have been assessed for tumor response at 8 wks. All doses were well tolerated and no MDX-1106 related SAEs occurred. Two pts (treated at 3 and 10 mg/kg) developed arthritic symptoms requiring treatment, and 2 pts had an asymptomatic TSH elevation. Objective tumor responses (CR or PR) were not observed within 8 wks. Three pts had significant lesional regressions (1 NSCLC pt at 1 mg/kg, 2 MEL pts at 10 mg/kg). Five pts with SD or lesional regressions received retreatment. Biopsy of a regressing MEL lymph node metastasis showed a moderately increased CD8+ T cell infiltrate post treatment. PK and immunological evaluations are underway. Conclusions: The targeted maximum dose of 10 mg/kg of MDX-1106 was achieved without observing dose-limiting toxicities, and lesional tumor regressions were observed in 3 of 23 pts evaluated. An expansion cohort at 10 mg/kg is enrolling 15 additional pts. Therapy with MDX-1106 to enhance endogenous antitumor immunity, either alone or in combination with other therapeutic modalities, warrants further study.