Antitumor effects of interleukin-2 gene-modified fibroblasts in an orthotopic colon cancer model

Jpn J Cancer Res. 1999 Sep;90(9):1000-6. doi: 10.1111/j.1349-7006.1999.tb00848.x.


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).

MeSH terms

  • Animals
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / pathology
  • Colonic Neoplasms / therapy*
  • Disease Models, Animal
  • Female
  • Fibroblasts / metabolism
  • Fibroblasts / transplantation
  • Genetic Therapy*
  • Humans
  • Interleukin-2 / genetics
  • Interleukin-2 / metabolism
  • Interleukin-2 / therapeutic use*
  • Mice
  • Mice, Inbred BALB C
  • Transfection
  • Tumor Cells, Cultured


  • Interleukin-2