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

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

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  • 1Brain Tumor Laboratory, Roger Williams Medical Center, Providence, Rhode Island (P.S., S.S.); Department of Neurosurgery, Boston University School of Medicine, Boston, Massachusetts (B.T., K.W., E.B., P.S., S.S.); Department of Hematology & Hematopoietic Cell Transplantation, City of Hope Hospital, Duarte, California (C.E.B.).

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01082926 NCT01280552.

KEYWORDS:

IL13Rα2; glioblastoma; glioma; immunotherapy; toxin

PMID:
24723564
PMCID:
PMC4165413
DOI:
10.1093/neuonc/nou045
[PubMed - indexed for MEDLINE]
Free PMC Article
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