Description of Research

Skin cancer is one of the most common types of cancer in the United States, with melanoma being the most dangerous type. Cutaneous melanoma is responsible for more than 75% of skin cancer deaths. Melanomas are malignant tumors of melanocytes, cells found in the basal layer of the skin, the bowel, and the uveal tract of the eye. The main causes of melanoma are sun exposure and UV radiation. Current treatments for primary melanomas are curative. However, there are no effective treatments for metastatic disease and once melanomas metastasize, they are usually fatal. Because of the immune system’s ability to systemically respond to aberrant cells and microorganisms, immunotherapy is a promising approach for the treatment of disseminated, metastatic cancer. We are investigating the use of cell-based vaccines for activating tumor-reactive helper (CD4+) and cytotoxic (CD8+) T cells. CD4+ and CD8+ T lymphocytes are activated by two signals: an antigen-specific signal delivered by Major Histocompatibility Complex (MHC) molecules containing the antigenic peptide, and a costimulatory signal delivered by a costimulatory molecule such as CD80. CD4+ T cells respond to peptide-MHC class II complexes, while CD8+ T cells respond to peptide-MHC class I complexes. Activated CD4+ T cells release cytokines, such as IFNγ, that “help” activate CD8+ T cells, while activated CD8+ T cells can kill tumor cells. Previously we have developed a vaccine for uveal melanoma that activates uveal melanoma-specific CD4+ and CD8+ T cells. The vaccine consists of uveal melanoma cells that constitutively express MHC I molecules and are transduced with genes encoding MHC II and costimulatory molecules. Since uveal and cutaneous melanoma both originate from melanocytes, they may share common tumor antigens. We therefore hypothesize that uveal melanoma vaccines may activate tumor-specific T cells that cross-react with cutaneous melanoma cells. To test this hypothesis, peripheral blood mononuclear cells (PBMC) from healthy donors will be activated using uveal melanoma vaccines, and tested for cytolytic activity against cutaneous melanoma cells. If proven cross-reactive, the use of these vaccines in vivo may prove to be an effective treatment for cutaneous melanoma.