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 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 beta-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.
Division of Pathology, Chiba Cancer Center Research Institute, Chiba, Japan.
M
M
Kimura
Y
Y
Yoshida
M
M
Narita
K
K
Takenaga
T
T
Takenouchi
T
T
Yamaguchi
H
H
Saisho
S
S
Sakiyama
M
M
Tagawa
D000818:Animals; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006084:Graft Rejection / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016513:Mice, SCID; D010190:Pancreatic Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D010529:Peritoneal Cavity; D012190:Retroviridae / Q000235:genetics*; D014407:Tumor Cells, Cultured
D007376:Interleukin-2; D015847:Interleukin-4