Progress on Cancer Regression

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Science  25 Jul 2003:
Vol. 301, Issue 5632, pp. 439
DOI: 10.1126/science.301.5632.439c

The tolerance displayed by the immune system toward self tissues represents a major obstacle in the treatment of cancer by immunotherapy. The surface protein cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) has emerged as a primary target for overcoming unresponsiveness to tumors because it potently represses T cell activation and because inhibiting it has helped to improve tumor vaccination in animal models.

Phan et al. treated 14 patients suffering from progressive metastatic melanoma with a combination of antibody against human CTLA-4 and a vaccine incorporating two peptides derived from the gp100 melanoma-associated antigen. In three patients, measurable or complete regression of metastatic tumors was observed, as compared with no regression in patients treated with the vaccine alone in a previous trial. Autoimmune responses in tissues, including the skin and intestine, were also detected in six of the patients. Specific increase of reactivity to the vaccinating peptides was not detected in peripheral blood T cells, but an increased expression of activation markers was observed. Thus, these results hold promise for refining immunotherapy approaches in treating cancer. — SJS.

Proc. Natl. Acad. Sci. U.S.A. 100, 8372 (2003).

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