Our group has demonstrated the clinical promise of a whole-cell vaccine composed of irradiated but viable melanoma cells from three human melanoma cell lines (M10, M24, and M101). Because melanoma cells also can express receptors for cytokines currently used in invitro expansion and activation of dendritic cells, we hypothesized that the efficacy of a human whole-cell melanoma vaccine could be significantly increased by using these cytokines to upregulate vaccine expression of costimulatory molecules. This study's objective is to demonstrate the induction of significant immune responses in patients receiving a cytokine- modified M24 whole-cell vaccine for treatment of regional or distant metastatic melanoma. There are three specific aims: 1. To determine whether certain cytokines such as interleukin 4, granuloctye macrophage-colony stimulating factor, and tumor necrosis factor-alpha can upregulate expression of multiple costimulatory molecules (CD54, CD58, CD80, and CD86) on human melanoma cells. 2. To determine how the coexpression of multiple costimulatory molecules and tumor antigens on melanoma cells affects the activation of T cells, the induction of autologous tumor-specific cellular cytotoxicity, and induction of specific cytotoxic T cells against MAGE1, MAGE3, and tyrosinase peptide epitopes. 3. To determine if administration of a cytokine- modified melanoma cell vaccine can induce significant immunological responses, specifically delayed-type hypersensitivity, cellular cytotoxicity, and complement-dependent cytotoxicity, in HLA haplotype-matched melanoma patients.
