Over the past decade, knowledge of the way in which the immune system can be used to fight cancer has greatly increased. Not only have scientists learned that the immune system can recognize certain proteins on cancer cells, but they have used this knowledge to develop vaccines that may help prevent cancer recurrence.
Now, scientists at Memorial Sloan-Kettering Cancer Center in New York have demonstrated that a new DNA-based vaccine can successfully treat melanoma in mice. The investigators, who reported their findings in the September 16th 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 skin of the mice. The human protein differed just enough from its mouse counterpart to trick the immune system into producing a powerful immune assault. The immune cells attacked both the melanoma cells and the pigment cells (which share a protein called gp75 that is not found in other tissues).
Engineering the Immune System
"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, which also share specific proteins with their normal cell counterparts. "These DNA vaccines are unique because they can trigger immunity where other types of vaccines fail to stimulate an immune response," said Dr. Houghton, noting that they are easy to produce, handle, and store.
The mice were immunized with human DNA via a novel delivery system called a gene gun. Microscopic gold particles were coated with human DNA and injected into the skin of the mice using a burst of helium gas. Once inside the skin cells, the DNA triggered an immune response.
Mouse vs Human DNA
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 that had received mouse DNA, they found that the tumors were widespread and no immune response could be detected. However, in the mice injected with human DNA, the tumors had regressed by 86% and there was a marked immune response.
In addition to inducing an immune attack in the mice, researchers found that the human DNA also caused an autoimmunity reaction similar to vitiligo in humans: white patches on the otherwise dark fur of the mice. 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 the tumor spreading," said Dr. Houghton. "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. Houghtons team found that the mechanisms involved in immune responses against tumors vs autoimmunity against normal tissues were quite different. "This means that we may be able to vaccinate a patient against melanoma, and thus induce an immune response against the tumor while, at the same time, blocking any autoimmunity from ever occurring," explained Dr. Houghton.
Dr. Houghtons research team plans to begin clinical trials using DNA from mice in melanoma patients some time next year.