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We evaluated 11 patients with large B-cell lymphoma treated with a single lot of cemacabtagene ansegedleucel (cema-cel), an allogeneic anti-CD19 CAR T product. Despite receiving identical infusion products (IP), patients exhibited heterogeneous cema-cel expansion and clinical outcomes. Our integrated analyses using longitudinal T-cell receptor (TCR) \u03b2 sequencing, single-cell molecular profiling, and mixed lymphocyte reaction assays revealed that high frequencies of preexisting, recipient-derived alloreactive CD8+ T cells-mediated rapid CAR T rejection in nonexpanders. Furthermore, effector-like features, rather than stem\/central memory programs, drove robust clonal CAR T expansion consistently across expanders. We confirmed similar expansion patterns in two independent cohorts treated with a separate lot of cema-cel or an allogeneic anti\u2013B-cell maturation antigen (BCMA) CAR T product. These findings highlight distinct cell-extrinsic and cell-intrinsic mechanisms that influence allogeneic CAR T performance and provide insights to optimize donor selection, manufacturing, and product design.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance:<\/jats:title>\n                    <jats:p>Clinical adoption of allogeneic CAR T-cell therapies has been limited by poor CAR T-cell expansion in some recipients. Using patient samples, we elucidated the cell-extrinsic and cell-intrinsic mechanisms governing allogeneic CAR T-cell rejection and expansion. Our findings provide actionable strategies to improve allogeneic CAR T-cell efficacy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1158\/2159-8290.cd-26-0248","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T14:01:52Z","timestamp":1790344912000},"page":"OF1-OF18","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cellular and Molecular Mechanisms Determining Allogeneic CAR T-cell Rejection and Expansion"],"prefix":"10.1158","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4335-7942","authenticated-orcid":false,"given":"Andrew P.","family":"Jallouk","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04twxam07","id-type":"ROR","asserted-by":"publisher"}],"name":"The University of Texas MD Anderson Cancer Center 1 , Houston, Texas."},{"id":[{"id":"https:\/\/ror.org\/05dq2gs74","id-type":"ROR","asserted-by":"publisher"}],"name":"Vanderbilt University Medical 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California."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1958-9703","authenticated-orcid":false,"given":"Kristen","family":"Zhang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01at8a333","id-type":"ROR","asserted-by":"publisher"}],"name":"Allogene Therapeutics (United States) 3 , South San Francisco, California."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5979-9406","authenticated-orcid":false,"given":"Elvin J.","family":"Lauron","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01at8a333","id-type":"ROR","asserted-by":"publisher"}],"name":"Allogene Therapeutics (United States) 3 , South San Francisco, California."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3704-4616","authenticated-orcid":false,"given":"Paul 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