Combo Treatment Best for Melanoma, Advanced Ovarian Cancer

Tuesday, February 19, 2008; 1:00 PM

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TUESDAY, Feb. 19 (HealthDay News) -- Combining periodic infusions of antibodies with a widely used cancer vaccine appears to be more effective and less harsh with melanoma and advanced ovarian cancer patients than using either treatment on its own, a new study shows.

Besides demonstrating the potential usefulness of a vaccine-and-antibody approach, the study -- published online in this week's issue of the the Proceedings of the National Academy of Sciences -- suggests a way of refining treatments 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," study author Dr. Stephen Hodi, of Dana-Farber Cancer Institute in Boston, said in a prepared statement. "This suggests techniques for further focusing the immune system to attack the cancer with less 'fallout' for normal tissue."

Previous studies and clinical experience have shown that certain monoclonal antibodies increase the immune system's tumor-destroying activities in some patients but can also give patients serious inflammatory problems, such as severe diarrhea and rashes.

Hodi's research team focused on a molecular 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), acts as a kind of shut-off valve: When the receptor is stimulated, it causes the T-cells to become inactive, quieting the immune response. Blocking CTLA-4 with a monoclonal antibody offers a way to keep the immune response at full force.

The team looked at a cancer vaccine made from patients' own tumor cells. The tumor cells are irradiated so they stop growing, and a gene in inserted so they 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.