This project is aimed at elucidating the host immune response to malignant melanoma, and the role this response plays in the progression of tumor growth and metastatic spread. Tumor specific proteins produced by melanoma cells in vivo and in vitro are being studied, in order to determine the mechanism of their formation, to examine the impact of their expression on tumor growth, and to study the feasibility of utilizing their specificity for the immunoassay and immunotherapy of malignant melanoma. The control mechanisms involved in the regulation of pigment production in normal and in transformed melanocytes are also being characterized. The results indicate that various murine melanomas (of spontaneous, ultraviolet light induced, and chemically induced origin) share common cell surface antigens which are capable of eliciting a tumor rejection response; these antigens have a specificity restricted to melanoma cells. One melanoma tumor specific antigen has been purified to homogeneity and partially characterized; it is a glycoprotein of 65 kilodaltons, which has significant biochemical and immunological homology to serum albumin. This antigen has been shown to be effective in the immunization of mice against subsequent challenge with melanoma in transplantation assays, demonstrating the potential immunological significance of tumor specific antigen production to the progress of tumor growth. We have also produced monoclonal antibodies specific for the melanocyte specific enzyme, tyrosinase; these reagents cross-react with human tyrosinase and promise to be extremely useful for the identification of normal and transformed melanocytes in vivo and in vitro. They should further prove valuable for the study of cellular control mechanisms functional in the response of melanocytes to varying environmental stimuli which affect pigmentation, such as ultraviolet light and melanocyte stimulating hormone.
