Human Epidermal Growth Factor Receptor 2–Interleukin-13 Receptor subunit alpha-2 (HER2–IL13Rα2) (HER2–IL13Rα2)

The HER2–IL13Rα2 target refers to the simultaneous targeting of Human Epidermal Growth Factor Receptor 2 (HER2) and Interleukin-13 Receptor subunit alpha-2 (IL13Rα2), a strategy primarily developed for treating glioblastoma multiforme (GBM) (Hegde et al., 2016, J. Clin. Invest.). HER2 (UniProt P04626) is a receptor tyrosine kinase that promotes cell growth and is expressed in about 80% of GBM samples, while IL13Rα2 (UniProt Q14627) is a high-affinity decoy receptor for IL-13 that is overexpressed in over 75% of high-grade gliomas (Brown et al., 2016, NEJM). While these receptors do not typically form a natural complex, bispecific therapeutic agents such as tandem chimeric antigen receptor (TanCAR) T-cells are designed to bind both antigens, effectively inducing a functional heterodimerization on the tumor cell surface (Hegde et al., 2016). This dual-targeting approach is intended to mitigate 'antigen escape,' a common mechanism of resistance where tumor cells downregulate a single target to survive (Ahmed et al., 2017, JAMA Oncol.). By requiring the presence of either or both antigens for activation, these therapies aim to provide a more comprehensive and durable anti-tumor response in the heterogeneous environment of the brain. This target combination is currently being explored in clinical and preclinical studies to improve the efficacy and durability of immunotherapy for aggressive brain cancers (Baylor College of Medicine, 2016).

Other names

ErbB2-IL13RA2HER2/IL13Rα2Tandem HER2-IL13Rα2 targetHER2-IL13Rα2 complex

Simultaneous or independent binding of bispecific CAR-T cells to HER2 and IL13Rα2, inducing a functional heterodimerization of the receptors and triggering T-cell mediated cytotoxicity.