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 Le vaccin GVAX

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Date d'inscription : 23/02/2005

MessageSujet: Re: Le vaccin GVAX   Jeu 19 Juin 2014 - 17:18

Researchers at the Johns Hopkins Kimmel Cancer Center have developed and tested a vaccine that triggered the growth of immune cell nodules within pancreatic tumors, essentially reprogramming these intractable cancers and potentially making them vulnerable to immune-based therapies.

In their study described in the June 18 issue of Cancer Immunology Research, the Johns Hopkins team tested the vaccine in 39 people with pancreatic ductal adenocarcinomas (PDAC), the most common form of pancreatic cancer. The disease becomes resistant to standard chemotherapies and is particularly lethal, with fewer than 5 percent of patients surviving five years after their diagnosis.

PDACs do not typically trigger an immune response against the cancer cells that comprise, but with the help of a vaccine developed by Johns Hopkins researcher Elizabeth Jaffee, M.D., the scientists were able to "reprogram" tumors to include cancer-fighting immune system T cells.

The vaccine, known as GVAX, consists of irradiated tumor cells that have been modified to recruit immune cells to a patient's tumor. The researchers tested GVAX in combination with an immune modulator drug called cyclophosphamide, which targets a type of immune cell, called Tregs, that typically suppresses the immune response of certain T cells that destroy cancer.

The reprogramming is designed to make the tumors more vulnerable to other immune-modulating drugs that have been useful in fighting other cancers, said Jaffee, The Dana and Albert "Cubby" Broccoli Professor of Oncology at the Johns Hopkins University School of Medicine.

Jaffee and colleague, Lei Zheng, M.D., say the vaccine could potentially convert many types of tumors to a state where immunotherapies can have a much larger impact.

For example, Jaffee says, in certain melanomas, "we've tested immunotherapies that target T cells and have found a 10-30 percent response in cancers that naturally have the ability to trigger immune system responses, but there are few options for the other 70 percent of patients who barely or never respond to immunotherapies."

The researchers found that the vaccine created structures called tertiary lymphoid aggregates within the patients' tumor, structures that help regulate immune cell activation and movement. The aggregates, which appeared in 33 of the 39 patients treated with the vaccine, had surprisingly well-organized structures that do not typically appear in these types of tumors naturally, said Zheng, an assistant professor of oncology and surgery at the Johns Hopkins University School of Medicine. "This suggests that there has been significant reprogramming of lymphocyte structures within the tumor."

The aggregates could "really shift the immunologic balance within a tumor, setting up an environment to activate good T cells to fight the cancer, by tamping down Tregs," Jaffee said, "and such T cells would be educated to recognize the cancer proteins in that specific tumor environment."

The vaccine and the resulting lymphoid aggregates boosted the activity of several molecular mechanisms that, like Tregs, inhibit cancer-fighting immune cells. That may sound like a bad thing, but it actually provides many new potential targets within the tumor for immune-modulating drugs, Zheng explained.

The researchers' next study in PDAC patients will test a combination of GVAX and an antibody to PD-1, one of the immune-suppressing molecules that became more active after vaccination. "We think combinations of immune therapies will have the biggest impact," he says.


Des chercheurs de l'Université Johns Hopkins Kimmel Cancer Center ont développé et testé un vaccin qui a déclenché la croissance des nodules de cellules immunitaires dans les tumeurs pancréatiques, essentiellement reprogrammer ces cancers difficiles et les rend potentiellement vulnérables à des traitements immunitaires.

Dans leur étude décrite dans le numéro de Juin 18 de Cancer de recherche en immunologie, l'équipe de Johns Hopkins a testé le vaccin sur 39 personnes avec des adénocarcinomes canalaires pancréatiques (PDAC), la forme la plus commune de cancer du pancréas. La maladie devient résistant aux chimiothérapies standard et est particulièrement meurtrière, avec moins de 5 pour cent des patients ont survécu cinq ans après leur diagnostic.

PDAC ne déclenchent généralement pas une réponse immunitaire contre les cellules cancéreuses qui comprennent, mais avec l'aide d'un vaccin mis au point par l'Université Johns Hopkins chercheur Elizabeth Jaffee, MD, les scientifiques ont réussi à «reprogrammer» les tumeurs pour inclure les cellules du système T immunitaires lutte contre le cancer .

Le vaccin, connu sous le nom GVAX, est constituée de cellules tumorales irradiées qui ont été modifiés pour recruter des cellules du système immunitaire à la tumeur d'un patient. Les chercheurs ont testé GVAX en combinaison avec un médicament de modulateur immunitaire appelé cyclophosphamide, qui cible un type de cellule immunitaire, appelé Treg, qui supprime généralement la réponse immunitaire de certaines cellules T qui détruisent le cancer.

La reprogrammation est conçu pour rendre les tumeurs plus vulnérables à d'autres médicaments immunomodulateurs qui ont été utiles dans la lutte contre d'autres cancers, a déclaré Jaffee, Dana et Albert "Cubby" Broccoli Professeur d'oncologie à l'École de médecine de l'Université Johns Hopkins.

Jaffee et collègue, Lei Zheng, MD, disent que le vaccin pourrait convertir de nombreux types de tumeurs à un état où les immunothérapies peuvent avoir un impact beaucoup plus grand.

Par exemple, Jaffee dit, dans certains mélanomes, "nous avons testé immunothérapies qui ciblent les cellules T et ont trouvé une réponse 10-30 pour cent dans les cancers qui ont naturellement la possibilité de déclencher des réactions du système immunitaire, mais il ya peu d'options pour l'autre 70 pour cent des patients qui répondent peu ou jamais pour les immunothérapies ".

Les chercheurs ont constaté que les structures de vaccins créé appelés agrégats lymphoïdes tertiaires dans la tumeur des patients, des structures qui aident à réguler l'activation des cellules immunitaires et de mouvement. Les agrégats, qui figuraient dans 33 des 39 patients traités avec le vaccin, ont étonnamment structures qui ne figurent généralement pas dans ces types de tumeurs naturellement bien organisé, a dit Zheng, professeur adjoint de l'oncologie et de chirurgie à l'université Johns Hopkins de médecine. "Cela donne à penser qu'il y a eu une reprogrammation importante des structures de lymphocytes dans la tumeur."

Les agrégats pourraient "vraiment pencher la balance immunologique dans une tumeur, la mise en place d'un environnement d'activer les cellules de bons T pour combattre le cancer, par tasser Tregs», a déclaré Jaffee, "et ces cellules T serait instruit à reconnaître les protéines de cancer dans cet environnement spécifique de la tumeur. "

Le vaccin et les agrégats lymphoïdes résultant stimulé l'activité de plusieurs mécanismes moléculaires qui, comme Tregs, inhibent les cellules immunitaires qui combattent le cancer. Cela peut sembler une mauvaise chose, mais il apporte en fait de nombreuses nouvelles cibles potentielles au sein de la tumeur pour les médicaments immunomodulateurs, Zheng expliqué.

Prochaine étude, les chercheurs de chez PDAC permettra de tester une combinaison de GVAX et un anticorps de PD-1, l'une des molécules immunosuppresseurs qui sont devenus plus actifs après la vaccination. "Nous pensons que des combinaisons de thérapies immunitaires auront le plus grand impact», dit-il.

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MessageSujet: Re: Le vaccin GVAX   Mer 18 Juin 2014 - 16:42

Investigators study new cancer immunotherapy to help patients with advanced pancreatic cancer

Published on June 16, 2014 at 7:40 AM ·

Medical investigators at the Virginia G. Piper Cancer Center at Scottsdale Healthcare are studying a new cancer immunotherapy to see if it can successfully help patients with advanced pancreatic cancer.

Des chercheurs étudient une nouvelle forme d'immuno-thérapie pour voir s'ils ne pourraient pas aider les patients aux prises avec un cancer du pancréas.

The Phase 2B clinical trial of CRS-207 and GVAX Pancreas vaccines is open at Virginia G. Piper Cancer Center Clinical Trials at Scottsdale Healthcare, a partnership with the Translational Genomics Research Institute (TGen), where cancer patients are treated with promising new drugs.


La phase 2 d'un essai clinique de CRS-207 et du vaccin Gvax est ouverte


Participants in the study, named ECLIPSE (Efficacy of Combination Listeria/GVAX Immunotherapy in the Pancreatic Cancer Setting), will be randomized so patients receive only the CRS-207 vaccine, or that vaccine combined with the GVAX Pancreas vaccine and low doses of cyclophosphamide. A third group of patients will receive a standard chemotherapy.


Les participants de l'étude nommée ECLIPSE sera faite selon le hasard. Des patients recevront seulement le vaccin crs 207, ou la combinaison de GVAX et cyclophosphamide. Un troisième groupe recevra une chimio standard.

"This is a very innovative approach using immunotherapy to treat pancreatic cancer," explained Dr. Erkut Borazanci, M.D., M.S., medical oncologist and Drug Development Scholar at Virginia G. Piper Cancer Center Clinical Trials at Scottsdale Healthcare and the study's lead investigator.

C'est une approche innovante d'utiliser l'immunothérapie pour le cancer du


The CRS-207 vaccine is a weakened form of the bacteria, Listeria monocytogenes, that has been genetically modified to be safe for human use, while retaining its ability to stimulate the immune system. Specifically, CRS-207 has been engineered to stimulate an immune response against the tumor-associated antigen mesothelin, which is present at high levels on pancreatic cancer cells.


Le vaccin crs-207 est fait d'une forme bactérie affaiblie la listeria qui a été génétiquement modifiée pour être sécuritaire pour les humains tout en conservant ses propriétés pour stimuler le système immunitaire. Plus spécifiquement le crs-207 a été fait pour stimuler une réponse immunitaire contre l'antigène mesothelin qui est présent à des taux élevés dans les cellules cancéreuses du pancréas.[/b]

The GVAX vaccine is composed of genetically modified, inactivated pancreatic cancer cells that have been shown to stimulate the immune system's anticancer activity. The vaccine is given with a low-dose of a common cancer drug called cyclophosphamide to boost the effectiveness of the vaccine.

Le vaccin Gvax est composé de cellules pancréatiques cancéreuses inactivées qui ont démontré pouvoir activer le système immunitaire anti-cancer. Le vaccin est donné avec un médicament appelé cyclospamide pour le booster.[/b]


In a recently completed Phase 2A trial in 93 patients with advanced pancreatic cancer, survival was improved in patients who received the combination regimen of CRS-207, GVAX and cyclophosphamide (6.1 months), compared to 3.9 months for those who received only cyclophosphamide and GVAX. The immunotherapies were well-tolerated, with no serious treatment-related adverse side effects.

Virginia G. Piper Cancer Center Clinical Trials is among the first 11 centers in the United States participating in the study. The drug was developed by Aduro BioTech, Inc., a clinical-stage immunotherapy company located in Berkeley, Calif. A total of 240 patients are expected to be treated at more than 20 clinical trial sites in North America.

"If this study is successful, we hope that this form of immunotherapy will become widely available across the country to treat patients with advanced pancreatic cancer," added Dr. Borazanci.

Pancreatic cancer is difficult to treat and is the fourth leading cause of cancer-related death in the U.S. Tumors may grow in the pancreas without any early symptoms, which means that the disease is often in an advanced stage when it is diagnosed, and survival remains poor.

Virginia G. Piper Cancer Center Clinical Trials is known worldwide for its expertise in studying new treatments for pancreatic cancer.


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MessageSujet: Re: Le vaccin GVAX   Ven 17 Jan 2014 - 17:41

Combining two specific anti-cancer vaccines, rather than administering one as monotherapy, doubles the 1-year survival probability in patients with metastatic pancreatic ductal adenocarcinoma (PDAC), according to the results of a phase II study presented January 14, two days in advance of the American Society of Clinical Oncology’s (ASCO) 2014 Gastrointestinal Cancers Symposium.

La combinaison de deux vaccins anti- cancer spécifiques , plutôt que l'administration d'une monothérapie , double la probabilité de survie à 1 an chez les patients atteints de métastases pancréatiques adénocarcinome ( PDAC ) , selon les résultats d'une étude de phase II présentés 14 Janvier deux jours à l'avance de l'American Society of Clinical Oncology de ( l' ASCO ) 2014 cancers gastro-intestinaux.

Adding the immunotherapy CRS-207 to GVAX Pancreas, rather than giving GVAX alone, sparked the improvement, most markedly in patients who received at least two doses of GVAX and at least one dose of CRS-207, and in those who had received two or more prior treatment regimens, the study’s researchers found in the randomized study.

L'ajout de l'immunothérapie CRS 207 au GVAX pour le pancréas , plutôt que de donner GVAX seul, a suscité une amélioration plus marquée chez les patients qui ont reçu au moins deux doses de GVAX et au moins une dose de CRS- 207, et chez ceux qui avaient reçu 2 thérapeutiques ou plus avant, les chercheurs de l' étude ont constaté cela dans l'étude randomisée.

“This is the first time a randomized study has shown that immunotherapy is effective in pancreatic cancer. This study is just a first step, and we believe we’ll be able to take this approach further,” said lead study author Dung T. Le, MD, an assistant professor of Medicine at the Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center in Baltimore, Maryland. “Various chemotherapy drugs are used, but there are no standard treatment options for second- or third-line therapy in this setting. We’re excited these patients may soon have an alternative to chemotherapy that could come with fewer side effects.”

"Il s'agit de la première fois qu'une étude randomisée a montré que l'immunothérapie est efficace dans le cancer du pancréas. Cette étude n'est qu'une première étape , et nous croyons que nous serons en mesure d'obtenir davantage encore de cette approche ", a déclaré le principal auteur de l'étude. " Divers médicaments chimiothérapeutiques sont utilisés, mais il n'y a pas d'options de traitement standard pour le traitement de deuxième ou de troisième ligne dans ce contexte. Nous sommes ravis que ces patients pourraient bientôt avoir une alternative à la chimiothérapie qui pourrait venir avec moins d'effets secondaires ".

Advanced pancreatic cancer has a very poor prognosis, ASCO said in a written statement. The best reported median survival of 11 months comes from first-line treatment with the chemotherapy regimen FOLFIRINOX. However, due to its side effects, only the fittest patients qualify for this treatment, and reported survival with other chemotherapy regimens is lower, according to the statement. For patients whose disease progresses despite first-line treatment, the median survival ranges from 4 to 6 months with second-line therapy, and 2 to 4 months with third-line therapy.

The new study tested an innovative strategy designed to stimulate an immune response against pancreas tumor cells, potentially improving outcomes for such patients with a regimen that appears to be better tolerated than chemotherapy.

La nouvelle étude a testé une stratégie novatrice visant à stimuler une réponse immunitaire contre les cellules tumorales du pancréas, ce qui pourrait améliorer les résultats pour les patients avec un régime qui semble être mieux toléré que la chimiothérapie.

GVAX is made from two pancreatic cancer cell lines that are irradiated so that they secrete the protein GM-CSF, which stimulates the immune system. The drug is given intradermally after low-dose cyclophosphamide (CY), which inhibits regulatory T cells, Le explained. CRS-207 is composed of live-attenuated Listeria monocytogenes engineered to stimulate an immune response against the protein mesothelin, which is present at high levels on pancreatic cancer cells, the authors and ASCO wrote.

GVAX est fabriqué à partir de deux lignées de cellules de cancer du pancréas qui sont irradiés pour qu'ils sécrètent la protéine GM -CSF, qui stimule le système immunitaire. Le médicament est administré par voie intradermique, après une faible dose de cyclophosphamide ( CY ) , qui inhibe les cellules T régulatrices. Le CRS- 207 est composé de Listeria monocytogenes vivants atténués et modifiés pour stimuler une réponse immunitaire contre la protéine de la mésothéline qui est présent à des niveaux élevés sur les cellules du cancer du pancréas.

In mouse tumor models, the two types of vaccines have proved synergistic, and in a phase I study of CRS-207, three patients with PDAC who had received prior GVAX lived ≥15 months, the authors noted.

The study by Le et al included 90 patients with metastatic PDAC, the most common form of pancreatic cancer, who were randomly assigned 2:1 to treatment with two doses of CY/GVAX followed by four doses of CRS-207 (arm A), all three weeks apart for a 20-week course of treatment; or six doses of CY/GVAX every three weeks (arm B). Courses could be repeated. The primary endpoint was overall survival (OS), and secondary endpoints were safety and clinical and immune responses. Nearly all patients had received at least one prior course of chemotherapy, and 51% of them had received two or more prior regimens.

At a planned interim analysis, with a median follow-up of 7.8 months, the median OS was 6.1 months for the two-vaccine therapy compared with 3.9 months for therapy with GVAX (hazard ratio


= 0.59, two-sided log rank P = .03). About 24% of patients in arm A were still alive after 1 year, compared with 12% in arm B, Le said.

Among patients who received at least three doses of vaccine (about 70% of all patients), those in arm A who received two doses of GVAX and at least one dose of CRS-207 had a median OS of 9.7 months compared to 4.6 months for those who took three or more doses of CY/GVAX alone (HR = 0.53, two-sided log rank P = .03). Investigators observed stabilization of CA19-9, a tumor marker in PDAC, in 32% of patients in arm A versus 13% of patients in arm B.

Parmi les patients qui ont reçu au moins 3 doses de vaccin (70% de tous les patients) ceux du bras A qui a reçu 2 doses de GVAX et au moins une dose de CRS-207 ont eu une moyenne de survie de 9.7 mois comparé à 4.6 pour ceux qu iont reçu 3 doses ou plus de CY/Gvax seulement. Les chercheurs ont observé une stabilisation du CA19-9 , un marqueur du PDAC chez 32% des patients dans le bras A versus 13% dans le bras B.

Based on the benefit observed at this interim analysis, the study was stopped and patients were allowed to cross over from arm B to arm A.

L'étude a été arrêté et les patients du bras B ont été transféré pour avoir les médicaments du bras A

The side effects of the vaccine were relatively mild, resolved quickly, and did not get worse with each dose of treatment (as is often the case with chemotherapy), ASCO wrote. The side effects included local reactions after GVAX, and transient fevers, rigors, and lymphopenia after CRS-207, according to the authors.

“CY/GVAX followed by CRS-207 shows extended survival with manageable toxicity in previously treated metastatic PDA and warrants further study,” the authors concluded.

The GVAX/CRS-207 combination is also being looked at in other clinical studies. The researchers are about to launch a large phase II study that will compare the vaccine combination versus CRS-207 alone versus chemotherapy as second-line or greater therapy for metastatic pancreatic cancer, according to ASCO. They are also looking at combining GVAX/CRS-207 with immune checkpoint inhibitors such as ipilimumab and anti-PD-1/PD-L1. A study testing GVAX/ipilimumab as a maintenance treatment for patients whose disease became stable on FOLFIRINOX has recently opened. - See more at: http://www.onclive.com/conference-coverage/gcs-2014/Combined-Vaccines-Improve-Survival-in-Metastatic-Pancreatic-Cancer#sthash.2io6YWM3.dpuf


La combinaison est aussi étudiée dans d'autres études cliniques. Les chercheurs vont faire une phase II pour comparer la combinaison de vaccin avec CRS-207 seul et la meilleur thérapie de deuxième ligne disponible.

Ils veulent aussi combiner Gvax/CRS-207 avec un inbiteurs de checkpoint comme ipilimumab et  anti-PD1/PD-l1. Une étude testant Gvax/ipillumab comme traitement de maintenance pour les patients devenus stables avec  Folfirinox a été ouverte récemment.

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MessageSujet: Re: Le vaccin GVAX   Mer 12 Déc 2012 - 12:48


Aduro BioTech, Inc. announces completion of enrollment in the Phase 2 clinical trial of the sequential administration of two cancer vaccines, Aduro's CRS-207 and GVAX Pancreas Cancer Vaccine, in patients with metastatic pancreatic cancer (ClinicalTrials.gov Identifier: NCT01417000). Enrollment was completed eight months ahead of schedule.

Aduro biotech annonce la finalisation de la phase 2 d'un essai clinique qui porte sur l'administration séquentielle de 2 vaccins le crs-207 et le gvax contre le cancer du pancréas chez les patients avec un cancer métastasé. L.enrôlement a été complété 8 mois plus tôt que prévu.

"We believe the rate of enrollment demonstrates significant interest in this vaccine treatment from our clinical investigators and their patients and reflects the high-quality work and dedication of our clinical trial sites," said Dr. Dirk Brockstedt, Senior Vice President of Research and Development at Aduro.


The vaccine regimen has been administered in an outpatient setting and has been well-tolerated thus far with no serious or unexpected adverse events related to the study vaccines. A formal interim analysis of the safety and efficacy of the randomized, controlled trial is expected in the first quarter of next year.

Le régime de vaccins a été administré à des patients en externe et il a été bien toléré sans effet adverse sérieux. Une analyse plus formelle sera donnée au premier trimestre de 2013.

"We are optimistic that the results of this trial will reveal a promising new therapeutic option that can extend life and increase quality of life."

Nous sommes optimistes que les résultats de cet essai révéleront un option thérapeutique nouvelle et prometteuse qui pourra allonger la vie et améliorer sa qualité.

Source: Aduro BioTech, Inc.

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MessageSujet: Re: Le vaccin GVAX   Jeu 21 Fév 2008 - 12:11

(Feb. 21, 2008) — One of the shortcomings of a therapy that uses millions of identical antibodies to boost the immune system's attack on cancer cells is that many patients whose tumors recede in response to the treatment also experience serious inflammatory problems, such as severe diarrhea and rashes. In a new study, a team led by Dana-Farber Cancer Institute researchers shows that giving periodic infusions of such "monoclonal" antibodies to patients who have received a widely used cancer vaccine unleashes a strong immune response to tumors, with less-harsh side effects.

Dans une nouvelle étude, les chercheurs ont démontré que donnés des infusions périodiques d'anticorps monoclonal aux patients qui ont reçu un vaccin largement utilisé provoque une réponse forte du système immunitaire avec moinsd'effets secondaires.

The study, to be published online by the Proceedings of the National Academy of Sciences the week of Feb. 18, reflects efforts to untangle the benefits of monoclonal antibody therapy from its drawbacks, which result from a too-aggressive immune system assault on normal, healthy tissue. Besides demonstrating the potential usefulness of a vaccine-and-antibody approach, the new study suggests a way of refining treatment strategies even further, based on the biological events that antibody treatment sets in motion.

"We now have a better understanding of how the treatment works -- by increasing the ratio of tumor-killing to immune system-suppressing cells," says the study's lead author, Stephen Hodi, MD, of Dana-Farber. "This suggests techniques for further focusing the immune system to attack the cancer with less 'fallout' for normal tissue."

"nous avons une meillure compréhension de comment les traitements fonctionnent - en augmentant le ratio de certaines cellules" dit l'auter principal de l'étude "cela suggère des techniques pour cibler plus spécifiquement le système immuntaire pour qu'il attaque le cancer avec moins de ratés"

The study focused on a molecular socket, or receptor, on the surface of the immune system's CD4+ T cells, which guide an attack on infected or cancerous cells. The receptor, known as CTLA-4 (for cytotoxic T lymphocyte-associated antigen), functions as a kind of shut-off valve for CD4+ T cells: When the receptor is stimulated, it causes the T cells to become inactive, quieting the immune response. Blocking CTLA-4 with a monoclonal antibody -- a protein uniquely fit for the job -- offers a way to keep the immune response at full force.


Studies and clinical experience have shown that CTLA-4-targeting monoclonal antibodies do increase the immune system's tumor-destroying activities in some patients. But many of these patients also develop serious inflammatory conditions, raising the possibility that the therapeutic and harmful effects of the treatment are linked.

The current study involved a cancer vaccine made from patients' own tumor cells. The vaccine is created by removing tumor cells from the body, irradiating them so they stop growing, and inserting a gene that causes them to produce a protein called GVAX. When the cells are then re-infused into patients, GVAX acts like a siren to the immune system, prompting a more energetic attack on cancer cells throughout the body.

La présente étude implique un vaccin contre le cancer fait à partir des cellules du patient. Le vaccin est créé en prenan les cellulles du patient, en les irradiant pour qu'elles arrêtent de croitre et en leurs insérant un gène qui fait qu'elles produisent une protéine appelée GVAX. Quand les cellules sont réinjectées,elles provoquent une attaque plus énergique du système immunitaire.


Unfortunately, these results are rarely lasting. Most patients treated with the vaccine eventually die as their disease resumes its progress.

For that reason, researchers have begun studying whether combining GVAX vaccines with monoclonal antibody therapy could lengthen remissions, since blocking CTLA-4 could bolster the immune response spurred by the vaccine. And there was reason to think the combination could tamp down the inflammatory problems associated with antibody therapy alone.

Parce que la réction ne dure pas, les chercheurs ont pensé combiné ce vaccin GVAX avec une thérapie aux anticorps monoclonal pour allonger le temps de rémissions parce qu'en bloquant CTLA-4 la réponse immunitaire provoquée par le vaccin pourrait être meilleure. Et il y a des raisons de penser qu'une telle procédure réduirait les effets secondaires.

"Using a vaccine to provoke a stronger immune response to cancer may enable us to use lower levels of CTLA-4 blockers, which could reduce the severity of their side effects," Hodi explains.

In an earlier study, he and his colleagues demonstrated that a single infusion of anti-CTLA-4 antibodies caused extensive tumor destruction in all five metastatic melanoma and ovarian cancer patients who had previously been immunized with a GVAX vaccine.

Dans une étude précédente, les chercheurs ont démonté qu'une infusion d'anti-CTLA-4 a réussi a détruire plus longtemps les tumurs das 5 mélanomes métastasés (:peau) et chez des patientes avec un cancer de l' qui avaient été vacciné avec le GVAX auparavant.

The new study, a joint effort of Dana-Farber's melanoma program and Cancer Vaccine Center, tested the combination in a larger number of participants. Eleven melanoma patients were infused with a CTLA-4-blocking antibody (Ipilumimab (R)) one to four months after receiving GVAX, and every two to three months thereafter, as needed.

In contrast to previous, more intensive antibody doses, none of the patients had severe side effects, although they all developed mild, low-level inflammatory conditions (usually a rash that went away in a few days). Moreover, in eight of the participants, tumors throughout the body either receded or became stable. The three other patients experienced less dramatic improvements that became apparent after several months of therapy.
Similarly encouraging results were obtained in nine patients with advanced ovarian cancer, although two of them did develop severe inflammatory problems. Although large die-offs of tumor tissue were less common than in the melanoma group, some of the ovarian cancer patients did experience such results.

En contraste avec ce qui se passait auparavant, aucun des patients n'a eu d'effets secondaires sévères même s'ils ont développé une forme de rash (irruption sur la peau). Toutefois les tumeurs ont soit diminuées soit devenues stables pour8 participants. Les 3 autres ont eu des détériotations de leurs conditions moins dramatques qu'on aurait pu s'y attendre qui sont devenues apparentes après plusieurs mois de thérapie. Même si pour le groupe des patientes avec un cancer de l'ovaire les régressions de tumeurs étaient m,oins apparentes, quelques une ont quand même expérimenté de telles régressions.

To understand what was happening at a basic cellular level, researchers studied tumor samples from six patients following antibody treatment. They found that tumor death was greatest in samples with high ratios of CD8+ T cells -- the foot soldiers of immune system attack -- to FoxP3+ regulatory T cells, which can reduce the immune response.

"Our results suggest that combination therapies of GVAX vaccine and CTLA-4-blocking antibodies could be enhanced by agents that target regulatory T cells such as FoxP3+," remarks Hodi, who is also an assistant professor of medicine at Harvard Medical School. "Future work will focus in that direction."

"Nos résultats démontrent que la combinaison du vaccin GVAX avec les anticorps bloquant le CTLA-4 pourrait être amélior avec des agents qui ciblent les cellules T régulières comme Foxp3+ et nous allons orienter nos recherches dans ce sens."
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MessageSujet: Re: Le vaccin GVAX   Sam 26 Aoû 2006 - 9:45

Cell Genesys Announces Publication of Encouraging Phase 1/2 Clinical Results For GVAX(R) Immunotherapy for Prostate Cancer in Early Stage Patients Before Receiving Hormone Therapy
SOUTH SAN FRANCISCO, Calif., July 5 /PRNewswire-FirstCall/ -- Cell Genesys, Inc. (Nasdaq: CEGE) today announced that the results from an initial clinical trial of GVAX(R) immunotherapy for prostate cancer in patients with early-stage disease have been published in a June issue of Clinical Cancer Research by a team led by Jonathan Simons, M.D., professor of Hematology and Oncology, Winship Cancer Institute, Emory University School of Medicine. The Phase 1/2 trial enrolled 21 patients with rising prostate specific antigen (PSA) levels following prostatectomy and who had not received any other treatment for their prostate cancer, including hormone therapy.

The results showed that 16 of 21 (76%) patients showed a statistically significant decrease in the rate of rise of PSA (PSA slope) post-treatment compared with the remaining five patients (p<0.001). One patient had a partial PSA response (>50% reduction of PSA) of 7-month duration. GVAX cancer immunotherapy was generally well tolerated, with self-limited injection site reactions, and mild flu-like symptoms being the most frequently reported side effects. In addition to clinical activity, the publication reported immunologic findings confirming that GVAX immunotherapy for prostate cancer resulted in the induction of immune responses as evidenced by the formation of antibodies directed against prostate cancer cells.
Les résultats montrent que 16 des 21 patients ont montré une décroissance statitisquement significative de PSA comparé avec les 5 patients restants. Un des patients a eu une réponse partielle du PSA (>50% réduction de PSA) de 7 mois. Le vaccin GVAX a été bien toléré avec des petites réactions au site de la piqûre et des sympômes analogues au rhume comme les symptômes rencontées le plus souvent.



Cell Genesys has completed five Phase 1 and Phase 2 clinical trials of GVAX immunotherapy for prostate cancer in approximately 200 patients with various stages of recurrent prostate cancer, and each trial has demonstrated a favorable safety profile. The initial Phase 1 /2 clinical trial in early- stage prostate cancer described in the above publication was conducted at Johns Hopkins Oncology Center. GVAX immunotherapy treatment was administered at a fixed dose in eight weekly intradermal injections in an outpatient setting. As noted above, one patient had a partial PSA response of 7-month duration which was associated with a corresponding decline in the tumor- associated marker, carcinoembryonic antigen (CEA), as well as induction of a high titer antibody response against a prostate cancer antigen. The titer of this antibody decreased when treatment ended, and subsequent tumor progression based on a rising PSA occurred. In addition, several candidate tumor- associated antigens recognized by treatment-induced antibodies were identified in the study, including antigens reported to be involved in modulation of immune response and cancer metastases.

"While our Phase 3 clinical trials and registration strategy for GVAX immunotherapy for prostate cancer are currently focused on the treatment of advanced prostate cancer, we are pleased to also obtain these encouraging results in an earlier-stage of the disease," said Joseph J. Vallner, Ph.D., president and chief operating officer of Cell Genesys. "We believe that GVAX immunotherapy for prostate cancer may have potential for the treatment of prostate cancer at various stages of the disease and we look forward to initiation of future label-expansion studies."

GVAX immunotherapy for prostate cancer is currently being studied in two Phase 3 clinical trials expected to enroll approximately 1200 patients with metastatic hormone-refractory prostate cancer (HRPC), comprising one of the largest Phase 3 clinical programs ever conducted in men with advanced prostate cancer. The first trial (VITAL-1) is enrolling chemotherapy naïve, asymptomatic patients without cancer-related pain and will compare GVAX cancer immunotherapy to Taxotere chemotherapy plus prednisone. The second trial (VITAL-2) is enrolling patients who are symptomatic with cancer-related pain and will compare GVAX cancer immunotherapy plus Taxotere to Taxotere plus prednisone. Each Phase 3 trial is expected to enroll 600 patients and is designed to demonstrate a survival benefit compared to Taxotere plus prednisone. Cell Genesys received Special Protocol Assessments (SPA) from the FDA for each of the VITAL-1 and VITAL-2 Phase 3 studies as well as Fast Track Status for the product itself.

The company's ongoing Phase 3 program is supported by the median survival results from two, independent, multi-center Phase 2 clinical trials in approximately 115 patients that are not only consistent with each other, but also compare favorably to the previously published median survival of 18.9 months for metastatic HRPC patients treated with Taxotere(R) (docetaxel) chemotherapy plus prednisone, the current standard of care. The Phase 3 program is designed to confirm this potential survival benefit for GVAX immunotherapy for prostate cancer.

Cell Genesys' GVAX cancer immunotherapies are whole-cell products which are designed to present the immune system with a broad spectrum of tumor antigens and stimulate an immune response against the patient's tumor. GVAX immunotherapy for prostate cancer is comprised of two prostate cancer cell lines that have been modified to secrete GM-CSF (granulocyte-macrophage colony stimulating factor), an immune stimulatory hormone which plays a key role in stimulating the body's immune response, and then irradiated for safety. GVAX cancer immunotherapy for prostate cancer is being developed as a non patient- specific, "off-the-shelf" pharmaceutical product.

Cell Genesys is focused on the development and commercialization of novel biological therapies for patients with cancer. The company is currently pursuing two clinical stage product platforms -- GVAX(R) cancer immunotherapies and oncolytic virus therapies. Ongoing clinical trials include Phase 3 trials of GVAX immunotherapy for prostate cancer, Phase 2 trials of GVAX immunotherapy for pancreatic cancer and leukemia, and a Phase 1 trial of CG0070 oncolytic virus therapy for bladder cancer. Cell Genesys continues to hold an equity interest in its former subsidiary, Ceregene, Inc., which is developing gene therapies for neurodegenerative disorders. Cell Genesys is headquartered in South San Francisco, CA and has its principal manufacturing operation in Hayward, CA. For additional information, please visit the company's website at www.cellgenesys.com.

Statements made herein about the company, other than statements of historical fact, including statements about the company's progress, results and timing of clinical trials and preclinical programs and the nature of product pipelines are forward-looking statements and are subject to a number of uncertainties that could cause actual results to differ materially from the statements made, including risks associated with the success of clinical trials and research and development programs, the regulatory approval process for clinical trials, competitive technologies and products, patents, continuation of corporate partnerships and the need for additional financings. For information about these and other risks which may affect Cell Genesys, please see the company's Annual Report on Form 10-K for the year ended December 31, 2005 filed on March 13, 2006 as well as Cell Genesys' reports on Form 10-Q and 8-K and other reports filed from time to time with the Securities and Exchange Commission. The company assumes no obligation to update the forward-looking information in this press release.
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Date d'inscription : 23/02/2005

MessageSujet: Le vaccin GVAX   Lun 27 Mar 2006 - 9:33



"Nous sommes contents d'avoir la possibilité de présenter les résultats de l'essai combiné de notre vaccin immuno-thérapique pour le cancer de la prostate et MDX-010, un anticorps qui stimules le système immunitaire qui a été développé pas nos colalborateurs à Medarex et Bristol Myers Aquibb. Nous sommes aussi contents de pouvoir fournir les dernières données sur notre vaccin immuno-thérapique sur la leucémie" a déclaré le docteur Joseph J. Vallner, président et chef opérateur de Cell Genesys. "nous continuons notre programmme d'essai en phase III de notre médicament principal pour le cancer de la prostate.

La présentation se fera en juin 2006 à l'asco (26 juin)


Dernière édition par Denis le Mer 12 Déc 2012 - 12:49, édité 1 fois
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