Significance of interleukin-13 receptor alpha 2-targeted glioblastoma therapy

Neuro Oncol. 2014 Oct;16(10):1304-12. doi: 10.1093/neuonc/nou045. Epub 2014 Apr 10.

Abstract

Glioblastoma multiforme (GBM) remains one of the most lethal primary brain tumors despite surgical and therapeutic advancements. Targeted therapies of neoplastic diseases, including GBM, have received a great deal of interest in recent years. A highly studied target of GBM is interleukin-13 receptor α chain variant 2 (IL13Rα2). Targeted therapies against IL13Rα2 in GBM include fusion chimera proteins of IL-13 and bacterial toxins, nanoparticles, and oncolytic viruses. In addition, immunotherapies have been developed using monoclonal antibodies and cell-based strategies such as IL13Rα2-pulsed dendritic cells and IL13Rα2-targeted chimeric antigen receptor-modified T cells. Advanced therapeutic development has led to the completion of phase I clinical trials for chimeric antigen receptor-modified T cells and phase III clinical trials for IL-13-conjugated bacterial toxin, with promising outcomes. Selective expression of IL13Rα2 on tumor cells, while absent in the surrounding normal brain tissue, has motivated continued study of IL13Rα2 as an important candidate for targeted glioma therapy. Here, we review the preclinical and clinical studies targeting IL13Rα2 in GBM and discuss new advances and promising applications.

Keywords: IL13Rα2; glioblastoma; glioma; immunotherapy; toxin.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / immunology
  • Clinical Trials as Topic
  • Disease Models, Animal
  • Exotoxins / therapeutic use
  • Glioblastoma / drug therapy*
  • Glioblastoma / immunology
  • Humans
  • Interleukin-13 / therapeutic use
  • Interleukin-13 Receptor alpha2 Subunit / immunology
  • Interleukin-13 Receptor alpha2 Subunit / therapeutic use*
  • Liposomes / therapeutic use
  • Mice
  • Molecular Targeted Therapy / methods
  • Recombinant Fusion Proteins
  • Treatment Outcome

Substances

  • Exotoxins
  • IL13-PE38
  • Interleukin-13
  • Interleukin-13 Receptor alpha2 Subunit
  • Liposomes
  • Recombinant Fusion Proteins