biostudies-literatureWilson TLNIAID NIH HHSNCI NIH HHSNIHNRSA-NIAIDNIH NCI2098-2119https://www.ebi.ac.uk/biostudies/studies/S-EPMC9437573biostudies-literatureUnknown12(9)Current chimeric antigen receptor-modified (CAR) T-cell products are evaluated in bulk, without assessing functional heterogeneity. We therefore generated a comprehensive single-cell gene expression and T-cell receptor (TCR) sequencing data set using pre- and postinfusion CD19-CAR T cells from blood and bone marrow samples of pediatric patients with B-cell acute lymphoblastic leukemia. We identified cytotoxic postinfusion cells with identical TCRs to a subset of preinfusion CAR T cells. These effector precursor cells exhibited a unique transcriptional profile compared with other preinfusion cells, corresponding to an unexpected surface phenotype (TIGIT+, CD62Llo, CD27-). Upon stimulation, these cells showed functional superiority and decreased expression of the exhaustion-associated transcCancer discoveryCommon Trajectories of Highly Effective CD19-Specific CAR T Cells Identified by Endogenous T-cell Receptor Lineages.PMC9437573P30CA021765F32 AI157296P30 CA021765R01 AI136514F32AI157296R01AI136514U01AI150747U01 AI150747Metais JYMettelman RCLockey TKim HAllen EKTalleur ACWilson TLGottschalk STriplett BMMinervina AAMeagher MMTrivedi SChou CHRiberdy JMPogorelyy MVCrawford JCVelasquez MPOlsen SRWillis CThomas PGLangfitt DKottapalli PfalseCommon Trajectories of Highly Effective CD19-Specific CAR T Cells Identified by Endogenous T-cell Receptor Lineages.Current chimeric antigen receptor-modified (CAR) T-cell products are evaluated in bulk, without assessing functional heterogeneity. We therefore generated a comprehensive single-cell gene expression and T-cell receptor (TCR) sequencing data set using pre- and postinfusion CD19-CAR T cells from blood and bone marrow samples of pediatric patients with B-cell acute lymphoblastic leukemia. We identified cytotoxic postinfusion cells with identical TCRs to a subset of preinfusion CAR T cells. These effector precursor cells exhibited a unique transcriptional profile compared with other preinfusion cells, corresponding to an unexpected surface phenotype (TIGIT+, CD62Llo, CD27-). Upon stimulation, these cells showed functional superiority and decreased expression of the exhaustion-associated transc2022-01-01T00:00:00Z2022 Sep2026-05-28T07:02:02.827Z2025-04-06T09:24:17.025ZS-EPMC94375733579280110.1158/2159-8290.CD-21-1508