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

1999; Wiley; Volume: 82; Issue: 4 Linguagem: Inglês

10.1002/(sici)1097-0215(19990812)82

1097-0215

Masaki Kimura, Yu Yoshida, Mitsuro Narita, Keizo Takenaga, Toshinao Takenouchi, Taketo Yamaguchi, Hiromitsu Saisho, Shigeru Sakiyama, Masatoshi Tagawa,

T-cell and B-cell Immunology

We have examined the anti-tumor effect in nude mice caused by human pancreatic cancer cells (AsPC-1) modified to secrete IL-2 or IL-4. Loss of tumorigenicity of cytokine-producing, but not wild-type, cells was observed despite their unaltered in vitro proliferation rates; and these anti-tumor effects were dependent on the amount of cytokine released. Wild-type cells inoculated into mice which had rejected IL-2- or IL-4-producer cells showed significant growth retardation, while no retardation was detected when unrelated human colon carcinoma cells were inoculated. Histological examination of regressing IL-2- or IL-4-producing AsPC-1 tumors in nude mice revealed infiltration by CD11b-, but not CD90-, positive cells around the tumors. Treatment of nude mice with anti-asialoGM1 antibody did not affect loss of tumorigenicity. 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-2, but not β-galactosidase, gene into mice which had wild-type cells in the peritoneal cavity also significantly prolonged survival. 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 conditions. An anti-tumor response can be induced by in vivo transfer of the IL-2 gene. Int. J. Cancer 82:549–555, 1999. © 1999 Wiley-Liss, Inc.