Characterization of a novel human tumor antigen interleukin-13 receptor alpha2 chain.

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.

• Authors: Koji Kawakami, Masaki Terabe, Mariko Kawakami, Jay A Berzofsky, Raj K Puri
• Journal: Cancer research (Cancer Res) Vol. 66 Issue 8 Pg. 4434-42 (Apr 15 2006) ISSN: 0008-5472 [Print] United States
• PMID: 16618770 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)

Chemical References

• Antibodies, Neoplasm
• Cancer Vaccines
• IL13RA1 protein, human
• Il13ra1 protein, mouse
• Interleukin-13 Receptor alpha1 Subunit
• Receptors, Interleukin
• Receptors, Interleukin-13
• Vaccines, DNA

Topics

• Animals
• Antibodies, Neoplasm (biosynthesis, immunology)
• B-Lymphocytes (immunology)
• CD4-Positive T-Lymphocytes (immunology)
• CD8-Positive T-Lymphocytes (immunology)
• Cancer Vaccines (administration & dosage, genetics, immunology)
• Female
• Humans
• Interleukin-13 Receptor alpha1 Subunit
• Killer Cells, Natural (immunology)
• Melanoma, Experimental (genetics, immunology, prevention & control, therapy)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Receptors, Interleukin (genetics, immunology)
• Receptors, Interleukin-13
• T-Lymphocytes, Cytotoxic (immunology)
• Transfection
• Vaccination (methods)
• Vaccines, DNA (administration & dosage, genetics, immunology)