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

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 alpha chain variant 2 (IL13R alpha 2). Targeted thepies against IL13R alpha 2 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 IL13R alpha 2-pulsed dendritic cells and IL13R alpha 2-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 IL13R alpha 2 on tumor cells, while absent in the surrounding normal brain tissue, has motivated continued study of IL13R alpha 2 as an important candidate for targeted glioma therapy. Here, we review the preclinical and clinical studies targeting IL13R alpha 2 in GBM and discuss new advances and promising applications.