Helping the Body Fight Prostate Cancer

Scientists have shown for the first time that a mouse's immune system can completely destroy cancerous prostate cells. Experts say the finding, published in today's issue of the Proceedings of the National Academy of Sciences, could open the door to an immune-based therapy for prostate cancer, the second most common cause of cancer-related death for men.

For the body's defense system to launch an attack against an invader, immune system cells called T cells must detect two different signals. "It's sort of like the two keys that need to be turned simultaneously to launch a nuclear missile," says Eugene Kwon, a urologist at the National Heart, Lung, and Blood Institute. When a cell turns cancerous, one of these signals--the antigen, a protein that the immune system regards as foreign--is expressed on the surface of the cancer cells themselves. The second signal, a protein called B7, is always present on the surface of so-called antigen-presenting cells that display the antigen to the immune system. This primes the T cells to attack all cells bearing the antigen, including the cancerous cells. But for reasons still not clear, some cancers, including prostate, don't activate a strong immune response.

To show that T cells in mice are able to mount a sustained attack against prostate cancer cells, Kwon and his colleagues made the cancer cells themselves express B7. (In essence, they bypassed the middleman, the antigen-presenting cells.) They extracted cancer cells from mice previously bred to develop prostate cancer spontaneously and added the mouse B7 gene so that the cells expressed the B7 protein. Within a week of injecting these cancer cells under the skin of normal mice, the tumor cells were completely destroyed by the T cells. After 90 days, the cancer cells had still not grown.

After this success, Kwon and his colleagues tried another approach: They turned off a T cell safety catch. Normally, T cells deactivate after a protein called CTLA-4 soaks up the B7 alarm signal. But if that happens before all the cancer cells are destroyed, the tumor is likely to recur. The researchers injected prostate cancer cells into healthy mice; then 7, 10, or 13 days later, they injected a protein that binds to CTLA-4, so that B7 would continue activating the T cells. The cancerous prostate cells in 42% of the mice (21 of 50) were completely eliminated by the immune system. The treatment significantly slowed the tumor growth in the rest of the mice. Because the effect of revving up the T cells is temporary, the mice didn't suffer autoimmune or inflammation problems.

"It's a sensible approach by serious immunologists," says Tom Waldman, a clinician at the National Cancer Institute. "I think they should go ahead with human trials." Team member James Allison, an immunologist at the University of California, Berkeley, says he hopes this strategy, probably used in conjunction with other treatments such as low-level chemotherapy, can be tested in humans within the next couple of years.

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