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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\u2212). Upon stimulation, these cells showed functional superiority and decreased expression of the exhaustion-associated transcription factor TOX. Collectively, these results demonstrate diverse effector potentials within preinfusion CAR T-cell products, which can be exploited for therapeutic applications. Furthermore, we provide an integrative experimental and analytic framework for elucidating the mechanisms underlying effector development in CAR T-cell products.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance:<\/jats:title>\n                    <jats:p>Utilizing clonal trajectories to define transcriptional potential, we find a unique signature of CAR T-cell effector precursors present in preinfusion cell products. Functional assessment of cells with this signature indicated early effector potential and resistance to exhaustion, consistent with postinfusion cellular patterns observed in patients.<\/jats:p>\n                    <jats:p>This article is highlighted in the In This Issue feature, p. 2007<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1158\/2159-8290.cd-21-1508","type":"journal-article","created":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T10:02:03Z","timestamp":1657101723000},"page":"2098-2119","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Common Trajectories of Highly Effective CD19-Specific CAR T Cells Identified by Endogenous T-cell Receptor Lineages"],"prefix":"10.1158","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2040-7655","authenticated-orcid":false,"given":"Taylor L.","family":"Wilson","sequence":"first","affiliation":[{"name":"1Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee."},{"name":"2Department of Microbiology, Immunology, and Biochemistry, University of Tennessee Health Science Center, Memphis, Tennessee."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0947-3149","authenticated-orcid":false,"given":"Hyunjin","family":"Kim","sequence":"additional","affiliation":[{"name":"1Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4365-7382","authenticated-orcid":false,"given":"Ching-Heng","family":"Chou","sequence":"additional","affiliation":[{"name":"1Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0941-5360","authenticated-orcid":false,"given":"Deanna","family":"Langfitt","sequence":"additional","affiliation":[{"name":"3Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tennessee."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3527-5616","authenticated-orcid":false,"given":"Robert C.","family":"Mettelman","sequence":"additional","affiliation":[{"name":"1Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9884-6351","authenticated-orcid":false,"given":"Anastasia A.","family":"Minervina","sequence":"additional","affiliation":[{"name":"1Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3067-751X","authenticated-orcid":false,"given":"E. 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