Antigen-specific T-cell receptor and Chimeric Antigen Receptor (TCR/CAR)

Antigen-specific T-cell receptors (TCRs) and Chimeric Antigen Receptors (CARs) are engineered molecular complexes used to redirect T-cell specificity toward specific antigens, primarily for cancer immunotherapy [1.1.1, 1.5.3]. TCRs are heterodimeric proteins that recognize processed peptide antigens presented by Major Histocompatibility Complex (MHC) molecules, enabling the targeting of both surface and intracellular proteins [1.1.4, 1.5.2]. Chimeric Antigen Receptors (CARs) are synthetic fusion proteins that combine an extracellular antigen-recognition domain (usually an antibody-derived scFv) with intracellular signaling motifs, allowing for MHC-independent recognition of cell-surface antigens [1.1.2, 1.5.1]. Upon binding to their cognate antigen, these receptors trigger robust T-cell activation, proliferation, and the release of cytotoxic granules and cytokines to eliminate target cells [1.1.1, 1.3.5]. While these technologies have achieved significant success in treating hematological malignancies, they pose unique clinical challenges, including systemic toxicities like cytokine release syndrome (CRS) and neurotoxicity [1.2.1, 1.2.2]. Ongoing research focuses on enhancing their persistence, overcoming the suppressive tumor microenvironment in solid tumors, and improving safety through the use of molecular switches and combination therapies with immunomodulators [1.3.1, 1.3.5].

Other names

T-cell receptorChimeric Antigen ReceptorTCR-TCAR-TSynthetic T-cell receptorEngineered T-cell receptorAntigen-specific TCRAntigen-specific CAR

Engineered receptors redirect T-cell specificity to recognize and eliminate cells expressing specific antigens. TCRs recognize peptide-MHC complexes, while CARs recognize surface antigens in an MHC-independent manner, both leading to T-cell activation, cytokine secretion, and direct cytotoxicity [1.1.1, 1.1.2, 1.5.3].