{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T06:47:16Z","timestamp":1793083636337,"version":"4.5.0"},"reference-count":45,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"21","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2025,7,20]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>We designed a CD19-targeted chimeric antigen receptor (CAR) comprising a calibrated signaling module, termed 1XX, that differs from that of conventional CD28\/CD3\u03b6 and 4-1BB\/CD3\u03b6 CARs. Preclinical data demonstrated that 1XX CARs generated potent effector function without undermining T-cell persistence. We hypothesized that 1XX CAR T cells may be effective at low doses and elicit minimal toxicities.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      In this first-in-human, phase I, dose escalation and expansion clinical trial, patients with relapsed or refractory large B-cell lymphoma received 19(T2)28z-1XX CAR T cells at four dose levels (DLs), ranging from 25 to 200 \u00d7 10\n                      <jats:sup>6<\/jats:sup>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Twenty-eight patients underwent apheresis and received CAR T cells. Sixteen and 12 patients were treated in the dose escalation and expansion cohorts, respectively. The overall response rate (ORR) was 82% and complete response (CR) rate was 71% in the entire cohort. The lowest dose of 25 \u00d7 10\n                      <jats:sup>6<\/jats:sup>\n                      was selected for dose expansion. In 16 patients treated at this DL, 88% achieved ORR and 75% CR. With the median follow\u2010up of 24 months, the 1-year event-free survival was 61% (95% CI, 45 to 82) and 14 patients remain in continuous CR beyond 12 months. In all cohorts, grade \u22653 cytokine release syndrome and immune effector cell\u2013associated neurotoxicity syndrome rates were low at 4% and 7%, respectively. 1XX CAR T-cell products contain a higher proportion of CD8 T cells with memory features, and CAR T-cell persistence has been detected beyond 1-2 years in patients with ongoing remission.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>The calibrated potency of the 1XX CAR affords excellent efficacy at low cell doses with favorable toxicity profiles and may benefit the treatment of other hematologic malignancies, solid tumors, and autoimmunity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco-24-02424","type":"journal-article","created":{"date-parts":[[2025,1,30]],"date-time":"2025-01-30T16:00:09Z","timestamp":1738252809000},"page":"2418-2428","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":21,"title":["Results From First-in-Human Phase I Study of a Novel CD19-1XX Chimeric Antigen Receptor With Calibrated Signaling in Large B-Cell Lymphoma"],"prefix":"10.1200","volume":"43","clinical-trial-number":[{"clinical-trial-number":"nct04464200","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2903-5130","authenticated-orcid":true,"given":"Jae H.","family":"Park","sequence":"first","affiliation":[{"name":"Cellular Therapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY"},{"name":"Department of Medicine, Weill Cornell Medicine, New York, NY"},{"name":"Center for Cell Engineering, Sloan Kettering Institute, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5099-9156","authenticated-orcid":true,"given":"M. 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