Protein- and DNA-based active immunotherapy targeting interleukin-13 receptor alpha2

Akiva Mintz, Denise M. Gibo, Achuthamangalam Madhankumar, Nancy M. Cladel, Neil Christensen, Waldemar Debinski

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)581-589
Number of pages9
JournalCancer Biotherapy and Radiopharmaceuticals
Volume23
Issue number5
DOIs
StatePublished - Oct 1 2008

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Interleukin-13 Receptor alpha2 Subunit
Interleukin-13 Receptors
Active Immunotherapy
DNA
Proteins
Astrocytoma
Glioma
Immunotherapy
Vaccines
Mortality

All Science Journal Classification (ASJC) codes

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Pharmacology
  • Cancer Research

Cite this

Mintz, Akiva ; Gibo, Denise M. ; Madhankumar, Achuthamangalam ; Cladel, Nancy M. ; Christensen, Neil ; Debinski, Waldemar. / Protein- and DNA-based active immunotherapy targeting interleukin-13 receptor alpha2. In: Cancer Biotherapy and Radiopharmaceuticals. 2008 ; Vol. 23, No. 5. pp. 581-589.
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Protein- and DNA-based active immunotherapy targeting interleukin-13 receptor alpha2. / Mintz, Akiva; Gibo, Denise M.; Madhankumar, Achuthamangalam; Cladel, Nancy M.; Christensen, Neil; Debinski, Waldemar.

In: Cancer Biotherapy and Radiopharmaceuticals, Vol. 23, No. 5, 01.10.2008, p. 581-589.

Research output: Contribution to journalArticle

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