Antitumor effects of interleukin-2 gene-modified fibroblasts in an orthotopic colon cancer model.
We transduced the interleukin-2 (IL-2) gene into murine fibroblasts BALBCL7 or murine colon cancer CT26 using a retroviral vector. BALBCL7 transduced with IL-2 gene secreted 748 pg/ml of IL-2, whereas IL-2 gene-modified CT26 secreted 1,167 pg/ml of IL-2 (48 h incubation, 1x10(6)/ml). Then, we inoculated gene-modified BALBCL7 and/or CT26 cells into BALB/c female mice, and observed the tumor growth. The tumor growth was inhibited in mice inoculated with parental CT26 plus IL-2 gene-modified BALBCL7, compared with that in mice given parental CT26 alone (P<0.01). Moreover, we investigated the cytotoxic activity of spleen cells derived from mice treated with gene-modified cells, and performed phenotypic analysis of the effector cells. The killer cells derived from mice inoculated with IL-2 gene-modified BALBCL7 plus parental CT26 showed higher cytotoxic activity than those from mice inoculated with CT26 alone. The cytotoxic activity was almost completely blocked by anti-CD8 antibody (Ab), and partially blocked by anti-asialo GM1 Ab. Next, we inoculated CT26 tumor tissue into murine cecum orthotopically, and treated the animals with gene-modified BALBCL7 plus parental CT26. The tumor size in the cecum was significantly decreased, compared with parental CT26 alone (P<0.01).
Terasawa
H
H
Second Department of Surgery, Wakayama Medical School.
Tanimura
H
H
Nakamori
M
M
Tsunoda
T
T
Iwahashi
M
M
Tani
M
M
Yamaue
H
H
D000818:Animals; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D004195:Disease Models, Animal; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000637:transplantation; D015316:Genetic Therapy; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D014162:Transfection; D014407:Tumor Cells, Cultured
D007376:Interleukin-2