Interleukin-13 receptor alpha 2-targeted chimeric antigen receptor signaling complex (IL13BBζ-CAR) (IL13BBζ-CAR)

The Interleukin-13 receptor alpha 2-targeted chimeric antigen receptor signaling complex (IL13BBζ-CAR) is a synthetic recombinant receptor engineered into T cells to treat high-grade gliomas, specifically glioblastoma multiforme (Brown et al., 2016, NEJM). The complex features an extracellular targeting domain composed of a mutated IL-13 ligand (E13Y), which selectively binds to the tumor-associated antigen IL13Rα2 while avoiding the more common IL13Rα1 receptor (Brown et al., 2015, Clin Cancer Res). Upon binding to the antigen on tumor cells, the intracellular 4-1BB (CD137) costimulatory domain and CD3ζ signaling domain are activated, triggering a robust immune response characterized by T-cell proliferation, cytokine secretion, and cytotoxic lysis of the cancer cells (Mustang Bio, 2023). The inclusion of the 4-1BB domain is intended to improve the metabolic fitness and long-term persistence of the T cells within the immunosuppressive tumor microenvironment of the brain (Pituch et al., 2018, Expert Opin Biol Ther). Furthermore, the engineered T cells co-express a truncated CD19 (CD19t) molecule, which serves as a non-signaling surface marker for the clinical-grade purification, tracking, and potential therapeutic depletion of the CAR T cells (Brown et al., 2016, NEJM). This signaling complex represents a precision medicine approach to redirecting cellular immunity against aggressive central nervous system malignancies.

Other names

IL13(E13Y)-BBζ-CD3ζ CARMB-101IL13Rα2-CARIL13-zetakine (4-1BB version)IL13BBζ/CD19t+ T-cell receptor

The CAR complex binds to IL13Rα2 on tumor cells via a mutated IL-13 ligand, triggering CD3ζ and 4-1BB signaling to induce T-cell mediated cytotoxicity (Brown et al., 2015, Clin Cancer Res).