Recent data indicate that 2 stimuli are required to activate T cells to proliferate and secrete cytokines. Signal 1 is provided by the T cell receptor, and the other requires interaction of other T cell surface receptors with their ligands on antigen presenting cells. In human melanoma, tumors from many pts. express the same tumor antigens, and peptides derived from these tumor antigens are often presented on tumor cell surfaces by MHC class I molecules HLA-A1 or A2. Thus, it may be possible to induce immunity against these shared melanoma antigens by vaccination with allogeneic tumor cell lines that express the tumor antigens, are HLA-A1 or HLA-A2 positive, and also express the appropriate costimulatory signals for T-cell activation. We introduced the gene encoding the T cell co-stimulatory molecule B7 (CD28 ligand) into 3 human melanoma cell lines that are HLA-A2+ (one is also HLA-A1+), express significant levels of LFA-3 and ICAM-1 and produce RNAs encoding the shared melanoma antigens MAGE-1 and -3, and tyrosinase. The objectives of the study are: 1) to determine the maximum number of B7-transfected allogeneic melanoma cells that can be administered SQ or ID, 2) to characterize the immune response to B7-transfected cells, and 3) characterize the toxicity, and observe any antitumor responses. Stage IV pts. will be typed for expression of HLA-A2 or HLA-A1. The 3 lines will be injected at 2 wk. intervals for 3 vaccinations on a rotating basis followed by 3 injections at monthly intervals. Cohorts of pts. will receive escalating doses of 10/7 cells and 10/8 cells SQ. A final cohort will receive 10/7 cells intradermally. We plan to accrue 50 pts. 17 pts. have been vaccinated. There has been 1 CR and no toxic reactions.
