The title of the project has been renamed. Last year's title was Immunogenicity of Melanoma. This project is focused on characterizing parameters important to the growth and differentiation of melanocytes and their significance to critical properties of transformed melanocytes (termed malignant melanoma) including their ability to grow as primary tumors and to metastasize. Our studies have identified, isolated and characterized melanogenic enzymes that regulate the quality and quantity of pigment produced within melanocytes; we have also characterized a melanosomal structural matrix protein. These proteins are encoded within a family of pigmentation-related genes that are specifically expressed by mammalian melanocytes. Interestingly, although expression of these genes is specific to pigment producing tissues, they are independently regulated following stimulation or inhibition of differentiation. The phenotypic and functional properties of the melanins produced by these regulatory catalytic controls differ dramatically, and effects on the functional and photoprotective properties of those melanins are being examined. We have also continued to characterize melanoma-specific antigens abnormally expressed by transformed melanocytes which play a role in immune responses to tumor growth; of interest is the fact that many of those antigens are normally expressed melanosomal specific proteins. Monoclonal antibodies to one of those antigens, termed B700, specifically cross-react with human melanoma and have proven useful as a highly specific probe for malignant melanoma. Intravenous treatment of tumor-bearing hosts with those antibodies provides significant protection against metastatic growth, and B700 constitutes the major immunodominant antigen in a melanoma vaccine that has proven to be efficacious for host survival in a novel model for spontaneous melanoma metastasis.
