Adenoviral Mediated Intra-Tumor Gene Transfer of Interleukin 23 Induces a Therapeutic Anti-tumor Response

摘要

IL-23 is a member of the IL-12 family of heterodimeric cytokines, comprised of p19 and p40 subunits, which exhibits immunostimulatory properties similar to IL-12. IL-23 has been shown to possess potent anti-tumor activities in several establishment models of cancer and a few therapeutic models, but the efficacy of local, adenoviral-mediated expression of IL-23 in established tumors has yet to be investigated. Here we have examined the anti-tumor activity of adenovirally-delivered IL-23 in a day 7 MCA205 murine fibrosarcoma tumor model. Three intratumoral injections of adenovirus expressing IL-23 (Ad.IL-23) significantly increased animal survival and resulted in complete rejection of 40 percent of tumors, with subsequent generation of protective immunity and MCA205-specific cytotoxic T-lymphocytes (CTLs). Additionally, we have shown that the anti-tumor activity of IL-23 is independent of IL-17, perforin and Fas ligand, but dependent on IFN-γ, CD4 and CD8 positive T-cells. These results demonstrate that direct intratumoral injection of adenovirus expressing IL-23 results in enhanced survival, tumor eradication and generation of protective immunity by generation of a Th1-type immune response.