{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T12:18:03Z","timestamp":1788351483470,"version":"build-2803163510"},"reference-count":44,"publisher":"BMJ","issue":"5","license":[{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"unspecified","delay-in-days":20,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University Hospital Tuebingen","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"DOI":"10.13039\/501100004176","name":"Miltenyi Biotec","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/501100004176","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2026,4,20]]},"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>CD19-directed chimeric antigen receptor (CAR) T-cell therapies have transformed the treatment landscape for pediatric B-cell acute lymphoblastic leukemia (B-ALL), yet relapses driven by antigen escape remain a major limitation. Dual-targeting CAR approaches recognizing CD19 and CD22 have shown promising clinical activity, but sustained remissions are limited by insufficient CAR T-cell persistence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>CAR22.19, a fully human tandem CD19\/CD22 CAR, was developed and administered under a named-patient program to nine heavily pretreated pediatric patients with relapsed or refractory B-ALL. Treatment indications were CD19-negative blast population (n=5), relapse after CD19 CAR T (n=3) and\/or restricted access to approved CAR T-cell products (n=3). Autologous and donor-derived CAR22.19 T-cells (CART22.19) were manufactured using a good manufacturing practice-compliant, semiautomated fresh-in-fresh-out process. Safety and efficacy were assessed through standardized clinical monitoring, measurable residual disease analysis, and CAR T-cell kinetics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Preclinical validation demonstrated antigen-specific cytotoxicity and dual antigen activity. Clinically, CART22.19 were well tolerated, with no treatment-related deaths and no grade \u22653 neurotoxicity, while grade \u22653 cytokine release syndrome occurred in 38.5% (5\/13) of infusions and resolved with standard interventions. An initial complete molecular remission was achieved in 78% (7\/9) of patients, with a 12-month overall survival rate of 55.6% (95% CI, 20.4-80.5%). Complete remission in CD19\u207bCD22\u207a disease underscores the functional contribution of the CD22-targeting domain, whereas all patients refractory to prior CD19 CAR T-cell therapy relapsed early despite retained CD19\u207aCD22\u207a expression. Limited in vivo persistence may represent a contributing factor to treament failure. Notably, durable remission and sustained functional persistence of CART22.19 was achieved in one patient refractory to autologous CART22.19 following infusion of donor-derived CART22.19 after reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (alloHSCT) in nonremission.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>CART22.19 therapy demonstrated a favorable safety profile and promising clinical activity in a high-risk pediatric population, with dual targeting enabling disease control in CD19-negative leukemia. Nonetheless, limited CAR T-cell persistence may represent an important obstacle to sustained remission. Our findings support further clinical development of CART22.19 and indicate that donor-derived CAR T-cells following RIC alloHSCT may represent a potential therapeutic strategy to enhance persistence and improve outcomes in heavily pretreated pediatric patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2025-013901","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T15:40:32Z","timestamp":1779378032000},"page":"e013901","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Human CART22.19 therapy in refractory pediatric B-ALL: insights from a named-patient 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