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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
Author(s) -
Kimura Masaki,
Yoshida Yu,
Narita Mitsuro,
Takenaga Keizo,
Takenouchi Toshinao,
Yamaguchi Taketo,
Saisho Hiromitsu,
Sakiyama Shigeru,
Tagawa Masatoshi
Publication year - 1999
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19990812)82:4<549::aid-ijc13>3.0.co;2-0
Subject(s) - biology , cancer research , cytokine , fibrosarcoma , pancreatic cancer , in vivo , genetic enhancement , microbiology and biotechnology , immunology , cancer , gene , genetics , biochemistry
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‐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 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.