Chimeric antigen receptor (CAR) (CAR)

A Chimeric Antigen Receptor (CAR) is a synthetic, engineered transmembrane protein designed to provide immune effector cells, typically T cells, with the ability to recognize and eliminate specific target cells, such as cancer cells, independently of the major histocompatibility complex (MHC) (June & Sadelain, 2018, NEJM). A CAR typically consists of an extracellular antigen-binding domain (usually a single-chain variable fragment or scFv), a hinge region, a transmembrane domain, and one or more intracellular signaling domains, such as CD3-zeta and costimulatory domains like 4-1BB or CD28 (Maus et al., 2014, Blood). By bypassing MHC restriction, CARs allow T cells to target a wide range of surface antigens that are not normally processed and presented (NIH NCI, 2024). In clinical practice, CAR-T cell therapies have revolutionized the treatment of B-cell malignancies by targeting antigens like CD19 and BCMA (FDA, 2023). However, the potent activation of the immune system by CAR-expressing cells can lead to significant toxicities, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) (Neelapu et al., 2018, Nat Rev Clin Oncology). Ongoing research focuses on expanding CAR technology to solid tumors and improving safety through switchable or logic-gated CAR designs to minimize off-tumor effects (Labanieh et al., 2018, Nature Biomedical Engineering).

Other names

Artificial T cell receptorChimeric T cell receptorChimeric immunoreceptorSynthetic T cell receptor

Chimeric antigen receptors (CARs) redirect T-cell specificity toward a surface antigen in an MHC-independent manner. Upon binding of the extracellular antigen-binding domain (scFv) to the target, the intracellular signaling domains (CD3-zeta and costimulatory domains like 4-1BB or CD28) initiate a signaling cascade that leads to T-cell activation, cytokine production, and cytotoxic degranulation, resulting in the lysis of the target cell (June & Sadelain, 2018, NEJM; Maus et al., 2014, Blood).