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Cancer Gene Ther. 2009 Oct;16(10):776-85. doi: 10.1038/cgt.2009.27. Epub 2009 Apr 24.

Adenoviral-mediated, intratumor gene transfer of interleukin 23 induces a therapeutic antitumor response.

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  • 1Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.

Abstract

Interleukin 23 (IL-23) is a member of the IL-12 family of heterodimeric cytokines, composed of p19 and p40 subunits, which exhibits immunostimulatory properties similar to IL-12. IL-23 has been shown to possess potent antitumor 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 antitumor 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% of tumors, with subsequent generation of protective immunity and MCA205-specific cytotoxic T lymphocytes. In addition, we have shown that the antitumor activity of IL-23 is independent of IL-17, perforin and Fas ligand, but dependent on interferon-gamma, CD4(+) and CD8(+) 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.

PMID:
19390568
[PubMed - indexed for MEDLINE]
PMCID:
PMC2745505
Free PMC Article
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