Novel FRET-based Immunological Synapse Biosensor for the Prediction of Chimeric Antigen Receptor-T Cell Function.

ABSTRACT: Chimeric antigen receptor (CAR)-T cell therapy has revolutionized cancer treatment. CARs are activated at the immunological synapse (IS) when their single-chain variable fragment (scFv) domain engages with an antigen, allowing them to directly eliminate cancer cells. Here, an innovative IS biosensor based on fluorescence resonance energy transfer (FRET) for the real-time assessment of CAR-IS architecture and signaling competence is presented. Using this biosensor, scFv variants for mesothelin-targeting CARs and identified as a novel scFv with enhanced CAR-T cell functionality despite its lower affinity than the original screened. The original CAR promoted internalization and trogocytosis, disrupting stable IS formation and impairing functionality are further observed. These findings emphas

SUBMITTER: Lee HN 

PROVIDER: S-EPMC11926508 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature