Characterization of a Novel Human Tumor Antigen

The interleukin (IL)-13 receptor A2 (IL-13RA2) chain is a primary binding and internalization subunit for a Th2-derived immune regulatory cytokine, IL-13. Although extremely high levels of IL-13RA2 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-13RA2 in tumor immunity, we used D5 melanoma cells stably transfected with the human IL-13RA2 gene (D5A2) to assess the effect of an IL-13RA2 DNA vaccine in immunocompetent animals. Prophylactic immunization of mice with the IL-13RA2 DNA vaccine resulted in protection against D5A2 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-13RA2 DNA vaccine showed a modest but significant inhibitory effect on D5A2 cells in vitro , suggesting that the antibody is biologically functional. The IL-13RA2 DNA vaccine also exhibited antitumor activity against established D5A2 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-13RA2 chain as a novel tumor rejection antigen. (Cancer Res 2006; 66(8): 4434-42)