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In situ adenoviral interleukin 12 gene transfer confers potent and long-lasting cytotoxic immunity in glioma

Cancer Gene Therapy volume 9, pages 9–15 (2002)Cite this article

Abstract

Interleukin 12 (IL-12) is a cytokine that promotes an antitumor Th1–type pattern of differentiation in mature naïve T cells. Despite its therapeutic success in multiple animal models of cancer, the utility of systemically administered recombinant cytokine has been limited by its toxicity. This has encouraged the development of local IL-12 delivery systems through gene transfer. To determine the effect of local adenoviral delivery of IL-12 on glioma immunogenicity, mice bearing GL-26 gliomas in the right corpus striatum were treated with direct intratumoral administration of AdmIL-12, AdLacZ, or normal saline. Survival was significantly prolonged in AdmIL-12–treated animals and immunohistochemistry demonstrated robust CD4+ and CD8+ T-cell infiltration in these mice compared to the two control groups. Glioma-infiltrating T lymphocytes from mice that received AdmIL-12 also demonstrated relatively increased, albeit statistically nonsignificant tumor killing. Based on IL-12's known ability to enhance Th1-type cytotoxic antitumor immune responses, we postulate our findings to be a result of localized induction of tumor immunity.

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Acknowledgements

This work was supported in part by National Institutes of Health (NIH) Grant NS02232 (to JS Yu).

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Authors and Affiliations

  1. Maxine Dunitz Neurosurgical Institute, Cedars Sinai Medical Center, Los Angeles, 90048, California, USA

    Yunhui Liu, Moneeb Ehtesham, Ken Samoto, Christopher J Wheeler, Reid C Thompson, Keith L Black & John S Yu

  2. Department of Molecular Biology and Biochemistry, University of California at Irvine, Irvine, 92697, California, USA

    Luis P Villarreal

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  1. Yunhui Liu
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Correspondence to John S Yu.

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Liu, Y., Ehtesham, M., Samoto, K. et al. In situ adenoviral interleukin 12 gene transfer confers potent and long-lasting cytotoxic immunity in glioma. Cancer Gene Ther 9, 9–15 (2002). https://doi.org/10.1038/sj.cgt.7700399

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