Melanomas that develop within the eye are treated by a variety of different methods that, in general, successfully control primary tumor growth. However, all of these treatments fail to alter the incidence of metastatic disease, which is unusually high and occurs in approximately 50% of patients with medium to large tumors. Although there is a long delay between the appearance of primary tumors and the development of secondary tumors, once metastatic tumors are clinically detectable, they grow rapidly, are resistant to conventional forms of therapy, and are universally fatal. There is currently no successful treatment available for patients with metastatic melanomas derived from ocular tumors. Previous studies indicate that ocular melanomas are immunogenic tumors that express tumor antigens recognized by specific T cells. Tumor-specific lymphocytes are present within the patient s peripheral blood and among tumor-infiltrating-lymphocytes. In order to successfully activate specific T cells, the PI proposes to use a form of gene therapy that increases the immunogenicity of primary ocular melanoma cells. The ultimate goal of this research is to develop a tumor cell vaccine that protects ocular melanoma patients from developing metastatic tumors. Protection is achieved by using primary tumor cells to stimulate tumor-specific T cells that eliminate metastatic tumor cells. He hypothesizes that primary tumor cells genetically engineered to express the costimulatory molecules B7.1 and interleukin-12 will stimulate tumor-specific cytotoxic T cells among the patient's peripheral blood lymphocytes. These lymphocytes will possess the ability to eliminate metastatic tumor cells. The first specific aim will determine if primary tumor cells that express costimulatory signals (B7.1 and/or interleukin-12) induce proliferation of autologous T cells. The second specific aim will determine if tumor-specific cytotoxic T cells are present among these proliferating cells, and the third specific aim will determine if these cytotoxic T cells lyse metastatic tumor cells.
