Vaccine, antibody combo effective for melanoma

March 4, 2008

Boston - A study conducted by researchers at Boston’s Dana-Farber Cancer Institute suggests that combining periodic infusions of antibodies with a commonly used cancer vaccine is more effective and less harsh for cancer patients, including those with melanoma, than using either treatment alone, HealthDay News reports.

Boston - A study conducted by researchers at Boston’s Dana-Farber Cancer Institute suggests that combining periodic infusions of antibodies with a commonly used cancer vaccine is more effective and less harsh for cancer patients, including those with melanoma, than using either treatment alone, HealthDay News reports.

The study’s authors note that in addition to demonstrating the potential usefulness of a combined vaccine and antibody approach, the research suggests a way to refine treatments, based on the biological events that antibody treatment sets in motion.

Published in a recent online issue of the Proceedings of the National Academy of Sciences, the study focuses on a molecular receptor on the surface of the immune system’s CD4+ T cells, which guide attacks on cancerous cells.

The receptor, known as cytotoxic T lymphocyte-associated antigen (CTLA-4), acts as a shut-off valve of sorts: When stimulated, it causes the T cells to become inactive, which lessens the immune response. Blocking CTLA-4 with a monoclonal antibody offers a way to keep the immune response fully active.

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

Researchers also looked at a cancer vaccine made from patients’ own tumor cells. The tumor cells are irradiated so that they stop growing, and a gene is then inserted so the cells produce a protein called GVAX.

When the cells are then re-infused into patients, GVAX prompts a more energetic attack on cancer cells throughout the body.

Since blocking CTLA-4 seems to bolster the immune response spurred by the vaccine, researchers studied whether combining GVAX vaccines with monoclonal antibody therapy could lengthen remissions and inhibit the inflammatory problems associated with antibody therapy alone.

The new study tested the combination on 11 melanoma patients, infusing them with a CTLA-4-blocking antibody one to four months after receiving GVAX, and every two to three months afterwards, as needed.

Compared with patients who received previous, more intensive antibody doses, none of the patients had severe side effects, though they all developed mild, low-level inflammatory conditions that disappeared in a few days.

In eight of the patients, tumors either receded or stabilized. The three other patients experienced improvements that were less dramatic.