Y. Iwanuma et al., INDUCTION OF TUMOR-SPECIFIC CYTOTOXIC T-LYMPHOCYTES AND NATURAL-KILLER-CELLS BY TUMOR-CELLS TRANSFECTED WITH THE INTERLEUKIN-2 GENE, Cancer immunology and immunotherapy, 40(1), 1995, pp. 17-23
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 th
eir growth rate compared with parental colon26 cells in vitro, but red
uced their tumorigenicity in vivo. Immunization with mIL2+colon26 cell
s could induce protective immunity against parental colon26 cells. Fol
lowing intravenous challenges, the colonies of lung metastasis were al
so inhibited. Moreover, inoculation of mIL2+ colon26 cells slowed the
growth of challenged renal cell carcinoma cells, RenCa. Intraperitonea
l inoculation of IL-2 gene transfectants generated a large number of p
eritoneal exudate cells and these cells had a highly cytolytic activit
y against colon26 and YAC-1. These results suggest that inoculation wi
th IL-2 transfected tumor cells can stimulate not only cytotoxic T lym
phocytes but also natural killer cells, and that these cells will act
as antitumor effector cells in host animals.