A Mousetrap for Cancer

Researchers have tricked a mouse's immune system into launching a vigorous attack against cancer cells. The body's natural defenses do not usually recognize tumor cells as foreign invaders and therefore do not attack them. But researchers at the Memorial Sloan-Kettering Cancer Center and Rockefeller University in New York report in the 10 December Proceedings of the National Academy of Sciences that when they injected a human version of a protein present in normal pigment cells into mice, the animals later mounted an immune response against skin cancer tumors. The researchers hope that the technique could help fight human cancers.

Immunologist Alan Houghton of Sloan-Kettering and his colleagues duped mouse immune systems into recognizing the protein gp75, which is normalaly present on the surface of melanocytes, the cells that produce skin pigment. Such cells can turn cancerous and cause the skin cancer melanoma. When the researchers injected the human version of the protein into the mice, the animals produced antibodies to it: The mice apparently identified the human protein as an invader. Those antibodies then recognized gp75 on mouse melanoma cells that the researchers injected into the animals, preventing the mice from developing tumors.

The only apparent side effect was the development of patchy white areas on the normally black mice. The patches eventually disappeared. But this effect indicates that the treatment had triggered an autoimmune response: The antibodies were indiscriminately targeting normal melanocytes as well as the malignant ones, says Houghton.

Houghton hopes that human immune systems can be primed to attack melanoma cells by injecting the mouse version of gp75. But immunologist Pramod Srivastava of Fordham University in New York City says that although the work is exciting evidence that antibodies can effectively target malignant tumors, the danger of autoimmune diseases such as arthritis might outweigh the benefits of such a treatment. "The burden," he says, "is to show that those dangers can be kept in line."

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