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

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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.

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Acknowledgements

This work was supported by grant CA100327 from the NIH.

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Authors and Affiliations

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

    J Reay, S-H Kim, E Lockhart & P D Robbins

  2. Department of Pediatrics, Childrens' Hospital of Pittsburgh, Pittsburgh, PA, USA

    J Kolls

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  1. J Reay
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  2. S-H Kim
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  3. E Lockhart
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  4. J Kolls
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  5. P D Robbins
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Correspondence to P D Robbins.

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Reay, J., Kim, SH., Lockhart, E. et al. Adenoviral-mediated, intratumor gene transfer of interleukin 23 induces a therapeutic antitumor response. Cancer Gene Ther 16, 776–785 (2009). https://doi.org/10.1038/cgt.2009.27

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  • DOI: https://doi.org/10.1038/cgt.2009.27

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