Expression of B7.1 (CD80) in a renal cell carcinoma line allows expansion of tumor-associated cytotoxic T lymphocytes in the presence of an alloresponse

We have selected a well-characterized human renal cell carcinoma (RCC) line as the basis for development of a genetically engineered tumor cell vaccin e to be applied in an allogeneic setting. This cell line was genetically mo dified by retroviral transduction to express B7.1 costimulatory molecules. The unmodified tumor cells and B7.1-expressing tumor cells were compared fo r their ability to induce tumor-associated responses in allogeneic peripher al blood mononuclear cells (PBMC) of two normal control donors having singl e MHC class I allele matches with the tumor cells. PBMC primed using B7.1-m odified tumor cells showed a preponderance of CD3(+)CD8(+) cytotoxic T lymp hocytes (CTL) that proliferated over extended periods of time in mixed lymp hocyte tumor cell (MLTC) cultures. Strong cytolytic activity developed in t he primed populations and included allospecific CTL with specificity for mi smatched HLA-A, -B and -C molecules. Nevertheless, it was possible to isola te CTL clones that were able to lyse tumor cells but not lymphoblastoid cel ls that expressed all the corresponding allospecificities. Thus, induction of complex allospecific responses did not hinder the development of fumer-a ssociated CTL in vitro. These results support the use of this genetically m odified allogeneic tumor cell line for vaccination of partial-MHC matched R CC patients.