August 2, 1999 -- By simultaneously stimulating the body's natural immune response and dampening a mechanism that normally protects the body from attack by its own immune cells, scientists have developed a promising technique for treating the most aggressive forms of the skin cancer melanoma. The new therapy may also work for prostate cancer.

"This two-pronged approach not only kills tumors in mice, but it also produces a characteristic response that we see in the few humans with aggressive melanoma who survive the disease, whether through therapy or spontaneous remission," said James Allison, a Howard Hughes Medical Institute investigator at the University of California, Berkeley. "This is a very exciting result, and we hope to begin human clinical trials by the end of the year."

Allison, who has been developing the new therapy for three years, reported his team's results in the August 2, 1999, issue of the Journal of Experimental Medicine. Andrea van Elsas and Arthur Hurwitz, postdoctoral fellows in Allison's laboratory, were co-authors of the paper.

Over the past decade, cancer researchers have found that tumor cells often bear molecules, or antigens, on their surfaces that the immune system can attack. But this last line of defense against cancer often fails because tumor cells can thwart this nascent immune response by becoming invisible to the immune system.

The tumor cell's cloaking ability rests with a molecule known as cytotoxic lymphocyte-associated antigen 4, or CTLA-4. This molecule, which healthy cells also produce, appears to stop the immune system's response to self cells.

"The body has elaborate controls that prevent the immune system from attacking its own body, otherwise we'd all develop autoimmune diseases," said Allison. "CTLA-4 is one of the regulatory molecules involved in this process." Other autoimmune diseases include rheumatoid ar
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Contact: Jim Keeley
keeleyj@hhmi.org
301-215-8858
Howard Hughes Medical Institute
2-Aug-1999