Characterization of a novel human tumor antigen interleukin-13 receptor α2 chain

The interleukin (IL)-13 receptor alpha 2 (IL-13R alpha 2) chain is a primary binding and internalization subunit for a Th2-derived immune regulatory cytokine, IL-13. Although extremely high levels of IL-13R alpha 2 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-13R alpha 2 in tumor immunity, we used D5 melanoma cells stably transfected with the human M-13R alpha 2 gene (D5 alpha 2) to assess the effect of an IL-13R alpha 2 DNA vaccine in immunocompetent animals. Prophylactic immunization of mice with the IL-13R alpha 2 DNA vaccine resulted in protection against D5 alpha 2 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-13R alpha 2 DNA vaccine showed a modest but significant inhibitory effect on D5 alpha 2 cells in vitro, suggesting that the antibody is biologically functional. The IL-13R alpha 2 DNA vaccine also exhibited antitumor activity against established D5 alpha 2 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-13R alpha 2 chain as a novel tumor rejection antigen.