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

Academic Article
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Overview

authors

  • Reay, J.
  • Gambotto, A.
  • Robbins, Paul D.

publication date

  • February 2012

journal

  • Cancer Gene Therapy  Journal

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.

subject areas

  • Adenoviridae
  • Animals
  • Cell Line, Tumor
  • Fibrosarcoma
  • Genetic Therapy
  • Genetic Vectors
  • Humans
  • Injections, Intralesional
  • Interleukin-12
  • Interleukin-23
  • Mice
  • Mice, Inbred C57BL
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Research

keywords

  • adenovirus
  • interleukin 12
  • interleukin 23
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Identity

PubMed Central ID

  • PMC3508719

International Standard Serial Number (ISSN)

  • 0929-1903

Digital Object Identifier (DOI)

  • 10.1038/cgt.2011.78

PubMed ID

  • 22158522
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Additional Document Info

start page

  • 135

end page

  • 143

volume

  • 19

issue

  • 2

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