Human Protein Dupes Immune System to Successfully Treat Melanoma in Mice

December 10, 1996

NEW YORK, N.Y., Dec. 10, 1996 -- Cancer cells pose a distinct problem for the immune system, whose sentinels destroy life-threatening pathogens but normally ignore the body¹s own cells. Despite their danger, tumor cells manage to evade attack because they share characteristics common to normal cells, a disguise that keeps the immune system at bay.

Now, scientists at Memorial Sloan-Kettering Cancer Center in New York have capitalized on that disguise to successfully treat the deadly skin cancer melanoma in mice, they report in the Dec. 10 issue of the Proceedings of the National Academy of Sciences. In a new strategy to battle cancer, the investigators injected into mice a human skin pigment protein that differed just enough from its mouse counterpart to trick the immune system into producing a powerful immune response. The immune cells attacked both skin pigment cells and melanoma cells in the mice, which share a protein called gp75 that does not exist in other cell types.

³The study clearly shows that it is possible to induce a strong immune response against the body¹s own cells that can lead to tumor rejection,² said lead author Dr. Alan N. Houghton, Chief of the Clinical Immunology Service at Memorial Sloan-Kettering. The same strategy may prove effective against breast, prostate, colon, and certain other cancers, each of which share specific proteins with a subset of normal cells.

For years, immunologists have tried to suppress abnormal immune attacks against the body¹s own cells, which occur when the immune system goes awry and lead to devastating autoimmune disorders such as multiple sclerosis, rheumatoid arthritis, and lupus. ³We¹re approaching autoimmunity from the opposite direction,² explained Dr. Houghton, a pioneer in the field of melanoma research and cancer vaccines. ³We want to induce a very controlled and temporary autoimmune response with the hope that it will lead to complete tumor rejection.²

The researchers first tried to induce an immune attack by injecting purified mouse gp75 alone or in combination with immune stimulators. But the mouse immune system simply would not respond to this ³self² protein.

The injection of human gp75 did not cause dangerous side effects, though the mice experienced a temporary skin depigmentation, which the researchers took as an encouraging sign. The mice developed a condition called vitiligo, which caused white patches to develop in their otherwise dark coats of fur. Vitiligo occasionally occurs in melanoma patients and is associated with a good outcome.

Dr. Houghton suspects that the injection of human gp75 induces an autoimmune response that prevents the tumor from spreading and, as a temporary side effect, destroys pigment cells. The dark coats of the mice were eventually restored after the injections were discontinued, but their tumors did not return.

Dr. Houghton is now conducting additional studies in animals to determine the feasibility of injecting slightly altered versions of human gp75 into melanoma patients. The research was funded by grants from the National Institutes of Health, the Louis and Anne Abrons Foundation, and the Swim Across America philanthropy.

Memorial Sloan-Kettering Cancer Center is the world¹s oldest and largest private institution devoted to prevention, patient care, research, and education in cancer. Throughout its long, distinguished history, the Center has played a leadership role in defining the standard of care for patients with cancer. In 1996, Memorial Sloan-Kettering was named the nation¹s best cancer center for the fourth consecutive year by U.S. News & World Report.

Memorial Sloan Kettering Cancer Center

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