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Characterization of a Novel Human Tumor Antigen Interleukin-13 Receptor 2 Chain

¹ Laboratory of Molecular Tumor Biology, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration; ² Vaccine Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland; and ³ Department of Advanced Clinical Science and Therapeutics, Graduate School of Medicine, University of Tokyo, Tokyo, Japan

Requests for reprints: Koji Kawakami, Department of Advanced Clinical Science and Therapeutics, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. Phone: 81-3-3815-5411 ext. 35642; Fax: 81-3-5800-9182; E-mail: kawakami-k{at}umin.ac.jp.

The interleukin (IL)-13 receptor 2 (IL-13R2) chain is a primary binding and internalization subunit for a Th2-derived immune regulatory cytokine, IL-13. Although extremely high levels of IL-13R2 chain are expressed on a variety of human tumor cells and specimens, its precise role in tumor immunology has not been defined. To investigate the role of IL-13R2 in tumor immunity, we used D5 melanoma cells stably transfected with the human IL-13R2 gene (D52) to assess the effect of an IL-13R2 DNA vaccine in immunocompetent animals. Prophylactic immunization of mice with the IL-13R2 DNA vaccine resulted in protection against D52 tumor development. In vivo depletion experiments in C57BL/6 and RAG-2 knockout mice indicated that both T and B cells, but not natural killer cells, were required for the tumor protection. In addition, antibody induced by the IL-13R2 DNA vaccine showed a modest but significant inhibitory effect on D52 cells in vitro, suggesting that the antibody is biologically functional. The IL-13R2 DNA vaccine also exhibited antitumor activity against established D52 tumors in mice. Histologic analysis of regressing tumors identified infiltration of CD4⁺ and CD8⁺ T cells and the expression of CXCL9 chemokine in tumors. Taken together, our results identify the human IL-13R2 chain as a novel tumor rejection antigen. (Cancer Res 2006; 66(8): 4434-42)

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