Acquired immunity in nude mice induced by expression of the IL-2 or IL-4 gene in human pancreatic carcinoma cells and anti-tumor effect generated by in vivo gene transfer using retrovirus

We have examined the anti-tumor effect in nude mice caused by human pancrea tic cancer cells (AsPC-1) modified to secrete IL-2 or IL-4. Loss of tumorig enicity of cytokine-producing, but not wild-type, cells was observed despit e their unaltered in vitro proliferation rates; and these anti-tumor effect s were dependent on the amount of cytokine released. Wild-type cells inocul ated into mice which had rejected IL-2 or IL-4-producer cells showed signif icant growth retardation, while no retardation was detected when unrelated human colon carcinoma cells were inoculated. Histological examination of re gressing IL-2- or IL-4-producing AsPC-1 tumors in nude mice revealed infilt ration by CD11b-, but not CD90-, positive cells around the tumors. Treatmen t of nude mice with anti-asialoGM(1) antibody did not affect loss of tumori genicity. Mice injected i.p. with IL-2- or IL-4-producing AsPC-1 cells did not die, in contrast to mice inoculated with wild-type cells. Injection of retrovirus-bearing IL-S but not P-galactosidase, gene into mice which had w ild-type cells in the peritoneal cavity also significantly prolonged surviv al. Thus, expression of the IL-2 or IL-4 gene in AsPC-1 cells may generate tumor-specific acquired immunity, even in mature T cell-deficient condition s. An anti-tumor response can be induced by in vivo transfer of the IL-2 ge ne. (C) 1999 Wiley-Liss, Inc.