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CHEMISTS ARE DEVELOPING VACCINE FOR SKIN CANCER
His CWRU co-investigators are Clifford Harding, professor of pathology, and Lili Liu, associate professor of oncology, both from the CWRU School of Medicine, with Stanton Gerson, professor of oncology, serving as the project's consultant. Melanoma occurs when tumors start to grow on clusters of the melanocytes that produce melanin or skin color. Sometimes these clusters appear as moles, which are benign. When moles turn darker or begin to grow, it is sometimes a sign of cancer and should be tested. While a researcher at the National Research Council in Canada before coming to CWRU two years ago, Guo worked on a project that developed a vaccine for leukemia. He plans to employ the same theories to the melanoma. "Developing vaccines for therapy is very popular now," Guo said. He points out that while the idea for cancer vaccines is more than 100 years old, it has seen a revival of interest. Instead of preventative vaccines, which are usually administered to protect against special bacterial diseases, Guo prefers the term immunotherapy to describe the cancer vaccines that clean up a disease after it appears. Once he can establish that procedure, he says that theory or process will have applications to other cancers as well. On the surface of cancer cells are abnormal tumor-associated carbohydrate antigens normally not found on non-cancerous cells. He likens these antigens to the cancer's fingerprint, which is different for each cancer. He said once researchers know the right antigens, they will have the key to unlocking a cure. In melanoma, these antigens are called GD2, GD3, GM2 and GM3. According to Guo, it is difficult to construct effective vaccines from these antigens directly because the immune systems of cancer patients develop immune tolerance to the natural antigens. Guo and his collaborators proposed a new strategy to get around the problem. How the new vaccine works, according to Guo, is to first boost the body's immune system with a synthetic vaccine made of an artificially modified TACA and then trigger the cancer cells to express this artificial antigen by treating the patient with a synthetic precursor. Because the synthetic antigen is foreign to the immune system, it does not have the immune tolerance that the naturally occurring TACAs have, and an immune response can be easily established to it. Once the tumor cells are marked by the modified TACA, the pre-stimulated immune system will react to them and wipe them out. In the lab, mice with melanoma are given the synthetic vaccine to boost the immune system. Researchers check the mice daily for their level of the immune response until the mice are primed to receive the precursor. Once administered, the precursor will be used by the cancer cells to present the modified antigen through their TACA biosynthetic machinery. Then the immune system goes to work. The prime goal of the project, Guo said, is to find the proper combination of the precursor and vaccine for melanoma.
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