Epidermal growth factor receptor and Interleukin-13 receptor subunit alpha-2 (EGFR and IL-13Rα2)

Epidermal growth factor receptor (EGFR) and Interleukin-13 receptor subunit alpha-2 (IL-13Rα2) are two distinct cell surface proteins that are frequently co-targeted in the treatment of high-grade gliomas, such as glioblastoma multiforme (UniProt P00533; UniProt Q14627). EGFR is a member of the ErbB family of receptor tyrosine kinases and plays a pivotal role in cell proliferation, survival, and migration through the activation of downstream signaling pathways like MAPK and PI3K/Akt (PubMed: 25227134). IL-13Rα2 is a high-affinity monomeric receptor for the cytokine IL-13; while it lacks the signaling motifs of the shared IL-13Rα1/IL-4Rα complex, it is significantly overexpressed in glioblastoma and contributes to tumor invasiveness (PubMed: 27932473). The rationale for targeting both molecules simultaneously, often through bivalent chimeric antigen receptor (CAR) T-cell therapy, is to combat the high degree of intratumoral heterogeneity and prevent antigen escape, which occurs when a tumor recurs after losing a single targeted antigen (Nature Medicine: 10.1038/s41591-024-02893-z). This dual-targeting strategy aims to provide a more robust and comprehensive anti-tumor response by ensuring that a larger population of tumor cells is recognized and eliminated by the immune system.

Other names

HER1ERBB1IL13RA2CD213A2Cancer/testis antigen 19CT19EGFRvIII

Dual-antigen targeting via chimeric antigen receptors or bispecific antibodies to enhance tumor specificity and overcome antigen escape in heterogeneous malignancies (Nature Medicine: 10.1038/s41591-024-02893-z).