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
✍ Scribed by Masaki Kimura; Yu Yoshida; Mitsuro Narita; Keizo Takenaga; Toshinao Takenouchi; Taketo Yamaguchi; Hiromitsu Saisho; Shigeru Sakiyama; Masatoshi Tagawa
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- French
- Weight
- 330 KB
- Volume
- 82
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
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 cytokineproducing, 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-2or 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-asialoGM 1 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 -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 celldeficient conditions. An anti-tumor response can be induced by in vivo transfer of the IL-2 gene.