. Therefore, a key question of CAR-T cell biology is why some cells persist whereas others perish. With this knowledge, we might better understand how to select patients, modify treatment phasing and optimize manufacturing protocols to support greater persistence and improve outcomes. To date, robust biomarkers of persistence have not been identified and can be validated only after directly demonstrating successful long-term persistence in patients.
We found that late-persisting CAR-T cells mainly comprised a population that did not express CD8-α or CD4 co-receptors transcriptionally or via surface expression. In healthy individuals, double-negative cells typically comprise a minor population of all T cells, and we observed similar proportions in non-CAR T-cells from the same patient. In general, there was a steady reduction in CD8CAR-T cells over time, which matched a progressive increase in double-negative populations.
Late-persisting CAR-T cells did not conform to quiescent early memory T cell populations but expressed genes associated with effector function and an activated state. These cells also maintained their proliferative capacity.
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