Induction of tumor-specific cytotoxic T lymphocytes and natural killer cells by tumor cells transfected with the interleukin-2 gene.

To study the antitumor effect of local production of interleukin-2 (IL-2) from tumor cells, the poorly immunogenic murine colon cancer cells, colon26, was transfected with murine IL-2 cDNA in a bovine papilloma virus vector. IL-2 gene transfectants (mIL2 + colon26) did not alter their growth rate compared with parental colon26 cells in vitro, but reduced their tumorigenicity in vivo. Immunization with mIL2 + colon26 cells could induce protective immunity against parental colon26 cells. Following intravenous challenges, the colonies of lung metastasis were also inhibited. Moreover, inoculation of mIL2 + colon26 cells slowed the growth of challenged renal cell carcinoma cells, RenCa. Intraperitoneal inoculation of IL-2 gene transfectants generated a large number of peritoneal exudate cells and these cells had a highly cytolytic activity against colon26 and YAC-1. These results suggest that inoculation with IL-2 transfected tumor cells can stimulate not only cytotoxic T lymphocytes but also natural killer cells, and that these cells will act as antitumor effector cells in host animals.