Anti-tumor effect of murine renal cell carcinoma cells genetically modified to express B7-1 combined with cytokine secreting fibroblasts.

Recently, many experiments have shown that the expression of the costimulatory molecule B7-1 on tumor cells can induce tumor-specific immunity. These results suggest that tumor cells modified to express costimulatory molecules can be used as a potential tumor vaccine. For this purpose, we transduced B7-1 gene into renal adenocarcinoma cells of spontaneous origin (Renca) in BALB/c mouse using the retroviral vector system. Our results indicated that approximately 60% of cells expressed B7-1 gene product using the retroviral vector system, and that B7-1 transduction did not affect the expression of MHC molecules on tumor cells nor the in vitro growth rate of tumor cells, but only in vivo tumorigenicity. As for the antitumor effect on the remote site, there were no significant differences among parental Renca, Renca lac Z and Renca B7-1 sublines, although tumors grew a little more slowly in the mice injected with Renca B7-1 cells as a vaccine. Even if the growth of tumors was significantly delayed in the mice treated by Renca B7-1 as a vaccine combined with the injection of BALB/c3T3 IL-12 near to the tumor on the same or following day, no significant antitumor effects were observed when the Renca B7-1 cells were injected as a vaccine compared with cytokines near the vaccine site. These results indicated that B7-1 gene transduction can decrease the tumorigenicity of murine renal cell carcinoma cells, but fails to induce sufficient antitumor response when it is used as a tumor vaccine. It is necessary to develop immunogenicity, by such means as irradiation or a combination of appropriate cytokines, to stimulate effective tumor immunity in a therapeutic setting.