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Cancer Res 2006 Apr 15;66(8):4434-42

Characterization of a Novel Human Tumor Antigen Interleukin-13 Receptor {alpha}2 Chain.

Kawakami K, Terabe M, Kawakami M, Berzofsky JA, Puri RK

Kawakami K, Univ Tokyo, Grad Sch Med, Dept Adv Clin Sci & Therapeut, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138655, Japan Univ Tokyo, Grad Sch Med, Dept Adv Clin Sci & Therapeut, Bunkyo Ku, Tokyo 1138655, Japan US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA NCI, Vaccine Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA

Abstract

The interleukin (IL)-13 receptor alpha2 (IL-13Ralpha2) chain is a primary binding and internalization subunit for a Th2-derived immune regulatory cytokine, IL-13. Although extremely high levels of IL-13Ralpha2 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-13Ralpha2 in tumor immunity, we used D5 melanoma cells stably transfected with the human IL-13Ralpha2 gene (D5alpha2) to assess the effect of an IL-13Ralpha2 DNA vaccine in immunocompetent animals. Prophylactic immunization of mice with the IL-13Ralpha2 DNA vaccine resulted in protection against D5alpha2 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-13Ralpha2 DNA vaccine showed a modest but significant inhibitory effect on D5alpha2 cells in vitro, suggesting that the antibody is biologically functional. The IL-13Ralpha2 DNA vaccine also exhibited antitumor activity against established D5alpha2 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-13Ralpha2 chain as a novel tumor rejection antigen. (Cancer Res 2006; 66(8): 4434-42).


Category: Journal Article, Peer
PubMed ID: #16618770
Includes FDA Authors from Scientific Area(s): Biologics
Entry Created: 2011-10-04 Entry Last Modified: 2012-08-29
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