DNA-Based Cancer Vaccine Shows Promise To Successfully Treat Melanoma In Mice

Now, scientists at Memorial Sloan-Kettering Cancer Center in New York have shown that a new DNA-based vaccine can successfully treat the deadly skin cancer, melanoma, in mice. The investigators, who report their findings in the September 15 issue of the Journal of Clinical Investigation, used a "needleless syringe" called a gene gun to drive tiny particles of human DNA at high speed into the mice's skin. The human protein differed just enough from its mouse counterpart to trick the immune system into producing a powerful immune attack. The immune cells attacked both the melanoma cells and the pigment cells in the skin of the mice, which share a protein called gp75 that is not found in other tissues.

"Our study shows how we can use DNA immunization to make the immune system recognize and attack cancer cells," said Dr. Alan Houghton, Chief of the Clinical Immunology Service at Memorial Sloan-Kettering and senior author of the study. The same strategy is being tested against prostate, breast and lymphoma cancers in mice, as they also share specific proteins with their normal cell counterparts.

"These DNA vaccines are unique because they can trigger immunity where other types of vaccines can fail to stimulate an immune response," added Dr. Houghton, noting that they are easy to make, handle and store.

The mice were immunized with human DNA via a novel delivery system called a gene gun, in which microscopic gold particles were coated with the human DNA and injected into the mice's skin using a burst of helium gas. Once inside the skin cells, the DNA triggered an immune response.

In the study, Dr. Houghton and his research team attempted to induce an immune attack by using the gene gun to immunize the mice with either a purified form of mouse DNA, or the human DNA. When the investigators later examined the lungs of the mice, they found that the tumors were widespread in those who had received the mouse DNA and could not detect an immune response.

However, the tumors had regressed by 86 percent in the mice injected with human DNA and the researchers found a marked immune response.

In addition to inducing an immune attack in the mice, the researchers found that the human DNA also caused autoimmunity, or a condition that occurs when the immune system attacks the body's own cells. The condition, called vitiligo in humans, caused white patches to develop on the mice's otherwise dark coats of fur. Vitiligo occasionally develops in melanoma patients and may be indicative of a good outcome.

"Our goal was to induce a very controlled autoimmune response that would lead to protection against tumor spreading," said Dr. Houghton, a pioneer in the field of melanoma research and cancer vaccines. "The human DNA induced an autoimmune response that prevented the tumor from spreading, and as a side effect, destroyed pigment cells."

Although immunologists know that autoimmunity can accompany an immune response, Dr. Houghton's team found that the mechanisms involved in immune responses against tumors versus autoimmunity against normal tissues were quite different.

"This means that we may be able to vaccinate a patient against melanoma, which would induce an immune response against the tumor while, at the same time, block any autoimmunity from ever occurring," explained Dr. Houghton.

Dr. Houghton's research team plans to begin clinical trials using DNA from mice in melanoma patients some time next year.

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Memorial Sloan-Kettering Cancer Center is the world's oldest and largest 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 standards of care for patients with cancer. In 1998, Memorial Sloan-Kettering was named the nation's best cancer center for the sixth consecutive year by U.S. News & World Report.

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