Immunological properties of tumor cells genetically modified to secrete interleukin-2

The immunological properties of interleukin-2 (IL-2) gene-transduced tumor cells were investigated in mice. A murine ovarian cancer cell line, OVHM, was retrovirally transduced with the human IL-2 gene (OVHM/IL-2) and the neomycin resistance gene (OVHM/Neo). OVHM/IL-2 cells continuously secreted IL-2 detected by ELISA using an antibody specific for human IL-2, and by a bioassay using an IL-2-reactive cell line (CTLL-2). When OVHM cells were inoculated subcutaneously into syngeneic B6C3F1 mice, OVHM/IL-2 cells but not parental (OVHM/P) or OVHM/Neo cells were regressed even though their rate of in vitro growth was comparable. This was not observed in nude mice, indicating the involvement of T lymphocytes in the regression of OVHM/IL-2 cells. The survival of mice inoculated intraperitoneally with OVHM/IL-2 cells was prolonged compared with those inoculated with OVHM/P cells. In irradiation experiments, IL-2 secretion by irradiated OVHM/IL-2 cells was retained for at least 5 days, although in vitro growth and in vivo tumorigenicity of irradiated OVHM/IL-2 cells were completely diminished. When mice were challenged with viable OVHM/P cells, survival of mice previously immunized with irradiated OVHM/IL-2 cells was prolonged compared to those immunized with irradiated OVHM/P cells, indicating a vaccine property of irradiated OVHM/IL-2 cells. Moreover, survival of mice with established ascites was improved upon injection of irradiated OVHM/IL-2 cells, indicating a therapeutic potential of OVHM/IL-2 cells. Tumor cells genetically engineered to secrete IL-2 may therefore be promising candidates for tumor vaccines and may provide a new mode of cancer immunotherapy.