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

J. Reay, S. H. Kim, E. Lockhart, J. Kolls, P. D. Robbins

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

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-γ, 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.

Original languageEnglish (US)
Pages (from-to)776-785
Number of pages10
JournalCancer gene therapy
Volume16
Issue number10
DOIs
StatePublished - Oct 2009
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by grant CA100327 from the NIH.

Keywords

  • Adenovirus
  • Fibrosarcoma
  • Gene therapy
  • Interleukin 12
  • Interleukin 23

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