Induction of systemic immunity by expression of interleukin‐23 in murine colon carcinoma cells

• Published in: International journal of cancer 2003-07, Vol.105 (6), p.820-824
• Main Authors: Wang, Yan‐Qing, Ugai, Shin‐ichi, Shimozato, Osamu, Yu, Ling, Kawamura, Kiyoko, Yamamoto, Hiroshi, Yamaguchi, Taketo, Saisho, Hiromitsu, Tagawa, Masatoshi
• Format: Article
• Language: English
• Subjects: Animal tumors. Experimental tumors; Animals; Biological and medical sciences; Carcinoma - immunology; Carcinoma - metabolism; Carcinoma - therapy; CD8-Positive T-Lymphocytes - immunology; Cell Division; colon carcinoma; Colonic Neoplasms - immunology; Colonic Neoplasms - metabolism; Colonic Neoplasms - therapy; Experimental digestive system and abdominal tumors; Gene Expression; gene therapy; Genetic Therapy; IFN‐γ; IL‐23; Interferon-gamma - biosynthesis; Interleukin-23; Interleukin-23 Subunit p19; Interleukins - genetics; Interleukins - metabolism; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; protective immunity; Transduction, Genetic; Tumor Cells, Cultured; Tumors
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.11160

Interleukin‐23 (IL‐23), a novel cytokine composed of a newly identified p19 molecule and the p40 subunit of IL‐12, can stimulate the proliferation in vitro of memory T cells. We examined whether Colon 26 murine colon carcinoma cells that were retrovirally transduced with the p19‐linked p40 gene (Colon 26/IL‐23) could produce antitumor effects in inoculated mice. The growth of Colon 26/IL‐23 tumors developed in immunocompetent mice was significantly retarded and the tumors disappeared thereafter. Spleen cells from the mice that received Colon 26/IL‐23 cells produced significant amounts of interferon‐γ, when they were cultured with irradiated Colon 26 but not irrelevant cells. Depletion of CD8+ T cells suppressed the production of interferon‐γ. The mice that had rejected Colon 26/IL‐23 tumors were resistant to subsequent challenge of parent but not irrelevant tumor cells. Colon 26/IL‐23 tumors were not rejected in nude mice but the growth was retarded compared to parent tumors. Treatment of nude mice with anti‐asialo GM1 antibody did not influence the growth of Colon 26/IL‐23 tumors. These data suggest that expression of IL‐23 in tumors produces T cell‐dependent antitumor effects and induces systemic immunity. © 2003 Wiley‐Liss, Inc.