Antitumor Effects of Interleukin‐2 Gene‐modified Fibroblasts in an Orthotopic Colon Cancer Model

• Published in: Cancer science 1999-09, Vol.90 (9), p.1000-1006
• Main Authors: Terasawa, Hiroshi, Tanimura, Hiroshi, Nakamori, Mikihito, Tsunoda, Takuya, Iwahashi, Makoto, Tani, Masaji, Yamaue, Hiroki
• Format: Article
• Language: English
• Subjects: Animals; Antitumor activity; Biological and medical sciences; CD8 antigen; Cecum; Colon cancer; Colonic Neoplasms - genetics; Colonic Neoplasms - pathology; Colonic Neoplasms - therapy; Colorectal cancer; Cytokine gene; Cytokines; Cytotoxicity; Disease Models, Animal; Effector cells; Female; Fibroblast; Fibroblasts; Fibroblasts - metabolism; Fibroblasts - transplantation; Gastroenterology. Liver. Pancreas. Abdomen; Gene therapy; Genetic Therapy; Humans; Interleukin-2 - genetics; Interleukin-2 - metabolism; Interleukin-2 - therapeutic use; Killer cells; Medical sciences; Mice; Mice, Inbred BALB C; Orthotopic model; Other treatments; Spleen; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Transfection; Treatment. General aspects; Tumor Cells, Cultured; Tumors
• ISSN: 0910-5050; 1347-9032; 1349-7006; 1876-4673
• 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, 1×106/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).