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The antitumor effects of adenoviral-mediated, intratumoral delivery of interleukin 23 require endogenous IL-12

Cancer Gene Therapy volume 19, pages 135–143 (2012)Cite this article

Abstract

Interleukin (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. We have demonstrated previously that adenoviral-mediated, intratumoral delivery of IL-23 (Ad.IL-23) was able to induce systemic antitumor immunity. Here we demonstrate that Ad.IL-23 requires endogenous IL-12 for conferring an antitumor effect after adenoviral-mediated, intratumoral delivery. In contrast, Ad.IL-12 does not require IL-23 for its antitumor effects although endogenous IL-23 appears important for induction of systemic antitumor immunity by IL-12. However, despite the requirement for endogenous IL-12, co-delivery of IL-23 and IL-12 does not provide even an additive local or systemic antitumor effect, regardless of the dose. We further demonstrate that although the use of a single-chain IL-23 (scIL-23) results in higher level of expression and a more pronounced IL-23-mediated antitumor effect, there is still no synergy with IL-12. These results demonstrate that although significant antitumor effects are achieved by intratumoral injection of adenovirus expressing either scIL-23 or IL-12 alone and that IL-23 requires endogenous IL-12 for maximum antitumor benefit, the combined use of these cytokines provides no additive or synergistic effect.

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Acknowledgements

This work was supported by Grants CA100327 and AR051456 from the National Institutes of Health to P.D.R.

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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, A Gambotto & P D Robbins

  2. Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    A Gambotto

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  1. J Reay
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  2. A Gambotto
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  3. P D Robbins
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Correspondence to P D Robbins.

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Reay, J., Gambotto, A. & Robbins, P. The antitumor effects of adenoviral-mediated, intratumoral delivery of interleukin 23 require endogenous IL-12. Cancer Gene Ther 19, 135–143 (2012). https://doi.org/10.1038/cgt.2011.78

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