Immunotherapy of Human Melanoma With Gene-Modified Tumor Cell Vaccines

The incidence of melanoma in the United States is increasing at a faster rate than that of any other cancer. The prognosis for metastatic disease is poor, and more effective treatments for disseminated disease are needed. Since melanoma is one of the more immunogenic tumors, strategies have focussed on immune recognition. In vitro studies suggest that potent tumor-specific cytotoxic T cells can be induced against human melanoma. Melanoma specific T-cell activation depends on appropriate presentation to the immune system of recently defined melanoma-associated antigens presented in the context of self-HLA gene products. Full T-cell activation requires the co- stimulation by B7-CD28 interactions at the T-cell surface and the elaboration of immune cytokines to promote T-cell growth. Data from animal models of tumor-specific immunization with tumor cells engineered to express immune cytokines or the B7 co-stimulatory molecule suggest that gene therapy for human melanoma may be an effective means to treat disseminated disease.