ADENOVIRAL TRANSDUCTION OF MELANOMA-CELLS WITH B7-1 - ANTITUMOR IMMUNITY AND IMMUNOSUPPRESSIVE FACTORS

Previous studies in experimental models have demonstrated that the tra nsduction of human or murine melanoma cells with the co-stimulatory B7 -1 molecule induces effective antitumor immune responses. In order to develop B7-1 gene transfer as a therapeutic tool in the clinical manag ement of melanoma, efficient means of in vivo gene transfer must be us ed. To this end we evaluated in vitro and in vivo immune responses ass ociated with adenoviral transduction-of murine and human melanoma cell s with B7-1. Adenovirus-mediated transduction of human and murine mela noma cells with B7-1 leads to high-level transgene expression in vitro and in vivo and does not affect MHC class I and II expression. Adenov irus-delivered B7-1 induced antitumor immune responses, on the basis o f observations that human melanoma cells transduced to express human B 7-1 were able to co-stimulate allogeneic and autologous T cells to pro liferate and that murine melanoma K1735 cells transduced to express mu rine B7-1 were rejected by syngeneic, immunocompetent mice. By contras t, intratumoral injection of an adenovirus encoding murine B7-1 failed to eliminate established murine melanoma (K1735) despite high-level t ransgene expression in tumor cells. Potent T cell inhibitory factor(s) secreted by both K1735 cells and select human melanoma cells may cont ribute to the failure to achieve protection in this setting. Thus, imm une inhibitory melanoma-derived factors need to be taken into account when considering the clinical use of B7-1 immunotherapy.