Phosphoproteomic analysis of successive Jurkat CD19-CAR generations reveals TCRζ-driven signalling.

ABSTRACT: Although chimeric antigen receptor (CAR) T cell therapy has revolutionised individualised cancer therapies for relapsed/refractory lymphomas, low long-term retention due to basal signalling (antigen-independent activation in the absence of cognate antigen) and off-target toxicity limit the broad applicability of CAR-T products. During CAR development, researchers use model systems, like Jurkat T cells (Jurkats), to screen intracellular signalling arrangements based on their ability to activate (e.g., CD69 expression) and withstand repeated antigen encounters. Although Jurkats are standard for CAR screening, the mapping of CAR generations to Jurkat-specific pTyr networks relative to key TCR nodes and CD69 readouts is not well defined, blurring how hierarchical signalling drives activation.

SUBMITTER: Callahan A 

PROVIDER: S-EPMC12664688 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature