{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T03:23:20Z","timestamp":1790306600704,"version":"4.1.0"},"reference-count":29,"publisher":"BMJ","issue":"4","license":[{"start":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T00:00:00Z","timestamp":1744761600000},"content-version":"unspecified","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016615","name":"Curing Kids Cancer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016615","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["5-K08-CA-277013"],"award-info":[{"award-number":["5-K08-CA-277013"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["5-P01-CA-214278"],"award-info":[{"award-number":["5-P01-CA-214278"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Susan S. and Stephen P. Kelly Center for Pediatric Cancer Immunotherapy at Children\u2019s Hospital of Philadelphia"},{"DOI":"10.13039\/100001422","name":"American Society of Hematology","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001422","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Emily Whitehead Foundation"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2025,4,1]]},"published-print":{"date-parts":[[2025,4]]},"abstract":"\n Background<\/jats:title>\n Relapse of B-cell acute lymphoblastic leukemia (B-ALL) with CD19-antigen loss after CD19-targeted chimeric antigen receptor (CAR) T-cell therapy has a dismal prognosis. Novel immunotherapeutic strategies for this patient population are urgently needed.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n We tested a novel, fully human anti-CD22\/4-1BB CAR T-cell construct, CART22-65s, in parallel phase I studies for pediatric and adult B-ALL. After lymphodepletion, CART22-65s was infused using a 3-day fractionated dosing scheme, allowing for omission of the second and third doses in cases of early cytokine release syndrome (CRS).<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Twenty-two patients, all with relapse after prior CD19-directed immunotherapy, were enrolled. Of 19 infused patients (pediatric, n=17; adult, n=2), 14 (74%) achieved a complete remission (CR), including 4 of 6 (67%) patients refractory to prior inotuzumab. Five of 14 patients in a CR proceeded to consolidative hematopoietic cell transplantation (HCT). With a median follow-up of 38 months, the 12-month relapse-free survival rate was 38.4% (95% CI 19.3% to 76.5%) and overall survival rate was 52.6% (95% CI 34.3% to 80.6%). Two patients received additional CART22-65s treatments for subsequent CD22-positive relapses; one achieved another CR. All CRS (n=17, 89%) and neurotoxicity (n=4, 21%) events after initial infusion were grades 1\u20132. The only grade 3 CRS\/neurotoxicity and the only high-grade immune effector cell-associated hemophagocytic lymphohistocytosis-like syndrome occurred in the retreatment setting. In vivo cellular kinetic data revealed robust CART22-65s proliferation by quantitative PCR peaking at a median of 20 days postinfusion, with the cells persisting out to month 42 in one patient who achieved a long-term remission with CART22-65s alone.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n The favorable safety profile and high remission rates in exceedingly refractory B-ALL support the continued development of CART22-65s but also highlight the need to use the product in combination with HCT or other novel strategies.<\/jats:p>\n <\/jats:sec>\n \n Trial registration numbers<\/jats:title>\n \n NCT02650414<\/jats:ext-link>\n and\n NCT03620058<\/jats:ext-link>\n .\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1136\/jitc-2025-011549","type":"journal-article","created":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T20:15:26Z","timestamp":1744920926000},"page":"e011549","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":24,"title":["CD22-targeted chimeric antigen receptor-modified T cells for children and adults with relapse of B-cell acute lymphoblastic leukemia after CD19-directed immunotherapy"],"prefix":"10.1136","volume":"13","clinical-trial-number":[{"clinical-trial-number":"nct02650414","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03620058","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct02650414","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct02588456","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct02650414","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03620058","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct05674175","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03620058","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct02650414","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03620058","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2542-2061","authenticated-orcid":false,"given":"Regina 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Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L","family":"Brogdon","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research Inc, Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clare","family":"Taylor","sequence":"additional","affiliation":[{"name":"Center for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie K","family":"Jadlowsky","sequence":"additional","affiliation":[{"name":"Center for Cellular Immunotherapies, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth O","family":"Hexner","sequence":"additional","affiliation":[{"name":"Center for Cellular Immunotherapies, University of Pennsylvania Perelman School of 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