T-cell exhaustion and CAR-T persistence
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).
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.
Pages like this
not linked directly; found by shared links- TechnologyLogic-gated therapeutics (AND, NOT gates)
Shares Antigen escape (antigen loss, lineage switch), Armoured, logic-gated & next-gen CARs, CAR-T cell therapy.
- PersonChristine E. Brown
Shares Armoured, logic-gated & next-gen CARs, CAR-T cell therapy.
- PersonRenier J. Brentjens
Shares Armoured, logic-gated & next-gen CARs, CAR-T cell therapy.
- PersonPawel Kalinski
- IdeaGD2 CAR-T as consolidation in high-risk neuroblastoma
Shares Armoured, logic-gated & next-gen CARs, CAR-T cell therapy.
- PersonJoseph Trapani
- TechnologyCAR-T against stroma: fibroblasts and myeloid cells
Shares Armoured, logic-gated & next-gen CARs, CAR-T cell therapy.
- CompanyArsenal Biosciences
Shares Armoured, logic-gated & next-gen CARs, CAR-T cell therapy.