T-cell receptor or chimeric antigen receptor engagement with tumor-associated antigens (TCR/CAR-TAA engagement)

T-cell receptor or chimeric antigen receptor engagement with tumor-associated antigens describes the critical interaction between an effector T-cell and a malignant cell. This process involves the binding of a T-cell receptor (TCR) to a peptide-MHC complex or a Chimeric Antigen Receptor (CAR) to a surface protein, which initiates a signaling cascade resulting in the formation of an immune synapse (June & Sadelain, 2018, NEJM). The subsequent activation of the T-cell leads to the secretion of perforins and granzymes, inducing apoptosis in the tumor cell (Labanieh & Mackall, 2023, Nature). While highly effective in treating certain leukemias and lymphomas, this engagement can also trigger systemic inflammatory responses such as Cytokine Release Syndrome (Brudno & Kochenderfer, 2019, Blood Reviews). This mechanism serves as the therapeutic foundation for adoptive cell transfer therapies, where T-cells are ex vivo modified to express receptors specific to tumor-associated antigens.

Other names

T-cell receptor-antigen interactionCAR-T cell engagementAdoptive T-cell therapy mechanismImmune synapse formationT-cell mediated cytotoxicity

Engineered or native receptors on T-cells bind specifically to tumor-associated antigens, triggering intracellular signaling that leads to T-cell activation, cytokine release, and direct lysis of the target tumor cell.