Induction and large-scale expansion of CD8(+) tumor specific cytotoxic T lymphocytes from peripheral blood lymphocytes by in vitro stimulation with CD80-transfected autologous melanoma cells

Human melanoma cell lines may induce a specific T cell response against tum or cells in vitro. However, after repeated restimulation with autologous tu mor cells, expansion of CTL is limited and often apoptosis of the T cells o ccurs. In order to improve conditions inducing primary T cell responses and thus allowing further expansion of tumor specific T cells for an adoptive transfer, we transfected human melanoma cells with the B7.1 gene (CD80), kn own to be a potent costimulatory molecule for T cell activation. CD80 expre ssion on melanoma cells resulted in improved primary T cell activation, esp ecially of CD8(+) T cells. Furthermore, restimulation with CD80(+) tumor ce lls gave rise to long term proliferating CD8(+) T cell lines demonstrating an 100-fold expansion of T cells compared to the 20-30-fold increased numbe rs obtained with the controls (parental tumor cells +/- anti-CD28). T cells stimulated with CD80(+) melanoma cells were found to display a MHC class I -restricted cytotoxic activity against autologous tumor cells. In conclusio n, these studies demonstrate the requirement of costimulation in generating large numbers of tumor specific T cells in vitro that may be used for an a doptive transfer in tumor immunotherapy.