Characterization of a novel human tumor antigen interleukin-13 receptor alpha2 chain.
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.
Kawakami
Koji
K
Laboratory of Molecular Tumor Biology, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland, USA. kawakami-k@umin.ac.jp
Terabe
Masaki
M
Kawakami
Mariko
M
Berzofsky
Jay A
JA
Puri
Raj K
RK
D000818:Animals; D000912:Antibodies, Neoplasm / Q000096:biosynthesis / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D005260:Female; D006801:Humans; D053661:Interleukin-13 Receptor alpha1 Subunit; D007694:Killer Cells, Natural / Q000276:immunology; D008546:Melanoma, Experimental / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018123:Receptors, Interleukin / Q000235:genetics / Q000276:immunology*; D053660:Receptors, Interleukin-13; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection; D014611:Vaccination / Q000379:methods; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
D000912:Antibodies, Neoplasm; D019496:Cancer Vaccines; C508181:IL13RA1 protein, human; C508183:Il13ra1 protein, mouse; D053661:Interleukin-13 Receptor alpha1 Subunit; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13; D019444:Vaccines, DNA