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Vaccine/antibody therapy effective, milder side effects in melanoma and ovarian cancer
Date:2/18/2008

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.

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.

"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.

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 mon
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Contact: Bill Schaller
william_schaller@dfci.harvard.edu
617-632-5357
Dana-Farber Cancer Institute
Source:Eurekalert

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