{"entity":{"id":"t-cell-exhaustion-term","kind":"term","name":"T-cell exhaustion and CAR-T persistence","aka":["exhaustion","exhausted T cells","T-cell fitness","T cell fitness","T-cell dysfunction","CAR-T persistence","CAR persistence","CAR-T expansion","peak expansion","in vivo expansion","B-cell aplasia","loss of persistence","memory phenotype","stem-like T cells"],"tldr":"Immune T cells that have been fighting too long become 'exhausted': sluggish, covered in inhibitory receptors, unable to kill. It limits both the patient's natural anti-tumour response and how long engineered CAR-T cells keep working (persistence).","summary":"Exhaustion is driven by chronic antigen exposure and marked by PD-1, TIM-3, LAG-3 and TOX expression; checkpoint inhibitors partly reverse it, which is their mechanism. For CAR-T, the fitness of the patient's starting T cells (damaged by prior chemotherapy, especially bendamustine) predicts expansion and response, and peak expansion and persistence correlate with durable remission; ongoing B-cell aplasia is a convenient marker that CD19 CAR-T cells are still active. Engineering answers include 4-1BB costimulation (longer persistence than CD28), armoured CARs, knockout of exhaustion-associated genes, and collecting cells earlier in the disease course. Persistence matters less when the tumour is eliminated quickly, as in ALL.","asOf":"2026-09-09","wikipedia":"https://en.wikipedia.org/wiki/T_cell_exhaustion","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/T_cell_exhaustion"}],"tags":[],"related":["antigen-escape","cold-vs-hot","hypogammaglobulinaemia"],"cancers":[],"sections":["cell-therapy","immunotherapy"],"technologies":["car-t","armored-car","checkpoint-inhibitor"],"targets":["pd1","lag3","tim3","tigit","cd57","cd69"],"drugs":["favezelimab","fianlimab","hlx26","relatlimab-nivolumab","azd7789","lb1410","cobolimab","hb0036","rilvegostomig","tiragolumab","domvanalimab","vibostolimab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["checkmate-142","checkmate-358","fianlimab-phase3-melanoma","i-spy-2","nct03486873","nct03899155","nct03916627","nct04082364","nct04165070","nct04524871","nct04590326","nct04626479","nct04626518","nct04655976","nct04665856","nct04736173","nct04895722","nct04931654","nct04938817","nct04995523","nct05009069","nct05123482","nct05211895","nct05224141","nct05287113","nct05329766","nct05417321","nct05489211","nct05502237","nct05565378","nct05608291","nct05625399","nct05633667","nct05645692","nct05676931","nct05702229","nct05724563","nct05775159","nct05785767","nct05787613","nct05800015","nct05805501","nct05845814","nct05904886","nct05970497","nct06062420","nct06101134","nct06109779","nct06161441","nct06190951","nct06205836","nct06246916","nct06264180","nct06342037","nct06349980","nct06357533","nct06467357","nct06468358","nct06472076","nct06521567","nct06561386","nct06564844","nct06627647","nct06692738","nct06697197","nct06727565","nct06764875","nct06769698","nct06787612","nct06865339","nct06868277","nct06921785","nct06943820","nct06963905","nct06989112","nct06996782","nct07058012","nct07069712","nct07098338","nct07115043","nct07221253","nct07224022","nct07281768","nct07431281","nct07492680","nct07720284","relativity-047","relativity-098"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Treatment jargon"},"route":"/terms/t-cell-exhaustion-term/","neighbours":{"term":[{"id":"antigen-escape","kind":"term","name":"Antigen escape (antigen loss, lineage switch)","route":"/terms/antigen-escape/"},{"id":"cold-vs-hot","kind":"term","name":"Hot vs cold tumours","route":"/terms/cold-vs-hot/"},{"id":"hypogammaglobulinaemia","kind":"term","name":"Hypogammaglobulinaemia and infection risk after B-cell therapies","route":"/terms/hypogammaglobulinaemia/"}],"section":[{"id":"cell-therapy","kind":"section","name":"Cell Therapy","route":"/fronts/cell-therapy/"},{"id":"immunotherapy","kind":"section","name":"Immunotherapy","route":"/fronts/immunotherapy/"}],"technology":[{"id":"armored-car","kind":"technology","name":"Armoured, logic-gated & next-gen CARs","route":"/technologies/armored-car/"},{"id":"car-t","kind":"technology","name":"CAR-T cell therapy","route":"/technologies/car-t/"},{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint 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