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

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 GM 1 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.