Unorthodox strategy: new cancer vaccine may thwart melanoma.

Efforts to enlist the immune system in the fight against cancer have generally yielded disappointing results. Scientists have yet to create a so-called cancer vaccine that reliably primes the immune system to recognize malignant cells and target them for destruction.

Having taken an unusual approach in their experiments on mice, researchers now report that destroying perfectly good skin cells can incite the immune system to kill the cancerous versions of these cells--with only modest side effects.

The potential treatment targets melanocytes, the cells that give skin its pigmentation. When malignant, these cells become melanoma, the deadliest form of skin cancer.

Although the experimental therapy would be a treatment for existing disease, the researchers refer to it as a cancer vaccine since it enlists the immune system to kill malignant cells, says study coauthor Gregory A. Daniels, a medical oncologist at the Mayo Clinic in Rochester, Minn.

This vaccine, administered to the mice in a series of injections, contains DNA plus an antiviral drug. In response to the treatment, the mice lost not only melanoma cells but also many healthy melanocytes, leaving the black mice with white splotches of hair that lasted for months. The findings appear in the September Nature Biotechnology.

For the experiment, Daniels and his colleagues implanted melanoma tumors in the mice. Starting 3 days later and continuing over the next 2 weeks the scientists injected the animals with two types of DNA and an antiviral drug called ganciclovir. One of the DNAs encodes a protein known to boost immune reactions; the other DNA encodes a viral enzyme.

"It's fortuitous that melanocytes seem to take up the DNA," Daniels says.

The mouse melanocytes then start making the viral enzyme and the immune-boosting protein, says Daniels. Ganciclovir latches onto the enzyme and kills the melanocytes.

The dying melanocytes "spill their contents," says Daniels, which include the immune-boosting protein and various other stress factors. These compounds set off a response by immune cells, which then zero in on and destroy other melanocytes and melanoma cells.

The mice remained free of tumors for at least 100 days after receiving the vaccine. Notably, the treatment destroyed tumors in areas away from the injection site. However, when the team implanted new tumors in the mice 100 days after the first batch of tumors had been eradicated, the protection had waned and the mice succumbed to melanoma.

The researchers traced the immune onslaught to shock troops known as CD8 T cells. The cancer vaccine didn't work in mice lacking such cells.

Other immune cells eventually suppress CD8 T cells, so the treatment isn't expected to continue to attack healthy melanocytes and, in that way, cause autoimmune disease.

These experiments are "very exciting," says cell biologist Mark E. Dudley of the National Cancer Institute in Bethesda, Md. "They indicate that the immune system is capable of seeing tumors and eliminating them under the appropriate conditions."

"The success rate of [previously tested] vaccines is less than 5 percent of treated patients," Dudley says. "New treatments are desperately needed." The incidence of melanoma is growing faster than any other cancer, with some estimates suggesting that 1 in 100 people in the United States can expect to develop melanoma at some time.

STATS

53,600

Estimated number of people in the United States diagnosed with melanoma per year