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Potent antitumor activity of IL-13 cytotoxin in human pancreatic tumors engineered to express IL-13 receptor α2 chain in vivo

Gene Therapy volume 10, pages 1116–1128 (2003)Cite this article

Abstract

Interleukin-13 receptor (IL-13R) α2 chain plays a key role in ligand binding and internalization. We have recently demonstrated that this cytokine receptor chain has unique characteristics in tumor biology: it inhibits tumorigenicity of breast and pancreatic cancer in animal models. In this study, we have exploited IL-13Rα2 chain and established a novel approach for pancreatic cancer therapy. For this, a plasmid encoding the IL-13Rα2 chain gene was mixed with liposomes and injected into subcutaneously or orthotopically xenografted human pancreatic tumors in immunodeficient mice, followed by systemic or local therapy by a recombinant IL-13 cytotoxin. Only tumors forced to express IL-13Rα2 chain acquired extreme susceptibility to the antitumor effect of IL-13 cytotoxin. There was a dominant infiltration of cells including macrophages and natural killer cells in the regressing tumors. Since macrophages were found to produce nitric oxide, IL-13Rα2-targeted cancer therapy involved not only a direct tumor cell killing by IL-13 cytotoxin but also activation of innate immune response at the tumor site. Therefore, this approach may be a new powerful tool for pancreatic cancer or other localized cancer therapy.

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Acknowledgements

We thank Ms P Dover for the procurement of reagents and laboratory supplies, and Dr RH Zaugg, Vical Inc. for kindly providing VR-1020 vector. We also thank Drs R Aksamit and N Markovitz of CBER/FDA for critical reading of this manuscript. These studies were conducted as part of a collaboration between the FDA and Neopharm Inc. under a Cooperative Research and Development Agreement (CRADA).

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  1. Division of Cellular and Gene Therapies, Laboratory of Molecular Tumor Biology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD, USA

    K Kawakami, M Kawakami, S R Husain & R K Puri

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Kawakami, K., Kawakami, M., Husain, S. et al. Potent antitumor activity of IL-13 cytotoxin in human pancreatic tumors engineered to express IL-13 receptor α2 chain in vivo. Gene Ther 10, 1116–1128 (2003). https://doi.org/10.1038/sj.gt.3301956

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