Protein- and DNA-Based Active Immunotherapy Targeting Interleukin-13 Receptor Alpha2

Abstract

High-grade astrocytoma (HGA) is an invariably fatal malignancy with a mean survival of 14 months despite surgery, radiation, and chemotherapy. We have found that a restricted receptor for interleukin-13 (IL-13), IL-13 receptor alpha 2 (IL13Rα2), is abundantly overexpressed in the vast majority of HGAs but is not appreciably expressed in normal tissue, with the exception of the testes. Therefore, IL-13Rα2 is a very attractive target for anti-HGA immunotherapy. In order to test protein and genetic vaccines that target IL13Rα2, we developed a G26-IL13Rα2-expressing syngeneic immunocompetent murine glioma model. Using this glioma model, mice were immunized with recombinant extracellular IL13Rα2 protein (IL13Rα2ex) or a DNA expression vector containing the gene for IL13Rα2 and were subsequently challenged with IL13Rα2(+) G26 tumors. Mice immunized with either recombinant or genetic IL13Rα2, but not mock-immunized controls, demonstrated complete protection against IL13Rα2(+) glioma growth and mortality. Of interest, only the recombinant-protein-based vaccines generated detectable anti-IL13Rα2 antibodies. These studies demonstrate the in vivo efficiency of protein- and DNA-based immunotherapy strategies that target IL13Rα2 that may play a clinical role to eradicate the residual microscopic HGA cells that inevitably cause disease recurrence and mortality.