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Adenovirus-mediated gene transfer of interleukin-23 shows prophylactic but not therapeutic antitumor effects

Cancer Gene Therapy volume 15, pages 693–702 (2008)Cite this article

Abstract

A novel cytokine interleukin (IL)-23 bears a structural and functional resemblance to IL-12. A recombinant adenovirus expressing IL-23N220L (recombinant replication-defective adenovirus (rAd)/IL-23N220L) that selectively secrets IL-23 was constructed and compared with rAd/IL-12N220L in terms of immunological and antitumor effects. In a prophylactic setting, vaccination with rAd/ovalbumin (OVA) and rAd/IL-23N220L enhanced OVA-specific CD8+ T-cell responses that were closely associated with complete protection against the subsequent challenge of OVA-expressing E.G7 thymoma. However, in a therapeutic setting, the intratumoral injection of rAd/IL-23N220L showed only marginal antitumor activity against several established tumors such as E.G7, CT26 and B16F10. Interestingly, whereas IL-23 still induced tumor-specific CD8+ T-cell responses, it could not activate natural killer (NK) cells in vitro and in vivo. In addition, the adoptive transfer of activated NK cells partially restored the therapeutic antitumor effect of IL-23, indicating that NK cells are one of the crucial factors responsible for the regression of established tumors. Taken together, we demonstrated that adenovirus-mediated gene transfer of IL-23 induces a potent prophylactic, but not a therapeutic, antitumor effect.

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Acknowledgements

We thank Sang-Chun Lee and Kwan Seok Lee for the dedicated animal care and Hong-Hwa Jun for the technical assistance. This study was supported by grants of SRC fund to IRC at University of Ulsan from the KOSEF and the Korea Ministry of Science and Technology and Technology Innovation Development Program, Small and Medium enterprises (SMEs; S0703222-C1449600-10000011) and Generic Technology Development Program, Minister of Commerce, Industry and Energy (10020817).

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  1. Research Institute, Genexine Co. Ltd, Seoul, Republic of Korea

    H-T Jin, S-Y Choi, S-H Yang & Y-C Sung

  2. Division of Molecular and Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea

    J-I Youn, S-H Seo, S-H Park, M-Y Song & Y-C Sung

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Correspondence to Y-C Sung.

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Jin, HT., Youn, JI., Choi, SY. et al. Adenovirus-mediated gene transfer of interleukin-23 shows prophylactic but not therapeutic antitumor effects. Cancer Gene Ther 15, 693–702 (2008). https://doi.org/10.1038/cgt.2008.41

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