{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:44:13Z","timestamp":1792799053860,"version":"4.5.0"},"reference-count":42,"publisher":"BMJ","issue":"5","license":[{"start":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:00:00Z","timestamp":1778803200000},"content-version":"unspecified","delay-in-days":14,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"HaiYa Young Scientist Foundation of Shenzhen University General Hospital","award":["HY002"],"award-info":[{"award-number":["HY002"]}],"id":[{"id":"https:\/\/ror.org\/01vy4gh70","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Program for Youzuzhikeyan of Shenzhen University","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"https:\/\/ror.org\/01vy4gh70","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Shenzhen Science and Technology Program","award":["JCYJ20241202124225031"],"award-info":[{"award-number":["JCYJ20241202124225031"]}]},{"name":"Shenzhen Medical Research Fund","award":["C2301003"],"award-info":[{"award-number":["C2301003"]}]},{"name":"Medicine Plus Program of Shenzhen University","award":["000003011601"],"award-info":[{"award-number":["000003011601"]}],"id":[{"id":"https:\/\/ror.org\/01vy4gh70","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Shenzhen Clinical Research Center for hematologic disease","award":["20230731103645009"],"award-info":[{"award-number":["20230731103645009"]}]},{"DOI":"10.13039\/501100017621","name":"Shenzhen Key Laboratory Foundation","doi-asserted-by":"crossref","award":["ZDSYS20200811143757022"],"award-info":[{"award-number":["ZDSYS20200811143757022"]}],"id":[{"id":"10.13039\/501100017621","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82030076"],"award-info":[{"award-number":["82030076"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82470229"],"award-info":[{"award-number":["82470229"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012151","name":"Sanming Project of Medicine in Shenzhen","doi-asserted-by":"crossref","award":["SZSM202111004"],"award-info":[{"award-number":["SZSM202111004"]}],"id":[{"id":"10.13039\/501100012151","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Shenzhen Natural Science Fund","award":["20200830182623001"],"award-info":[{"award-number":["20200830182623001"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2026,5,5]]},"published-print":{"date-parts":[[2026,5]]},"abstract":"\n Background<\/jats:title>\n Relapsed or refractory (R\/R) B-cell non-Hodgkin\u2019s lymphoma (B-NHL) remains a major therapeutic challenge despite CD19-directed chimeric antigen receptor (CAR) T-cell therapies, with treatment failure often driven by antigen escape and limited CAR-T persistence. Dual targeting of CD19 and CD20 may mitigate antigen loss. We conducted an expanded phase I\/II study of bispecific CD19\/20 CAR-T cells and incorporated spatially resolved single-cell transcriptomics to evaluate tumor-intrinsic and microenvironmental factors of clinical response.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Patients with R\/R B-NHL received CD19\/20 CAR-T cells following lymphodepletion. Efficacy, safety, CAR-T expansion\/persistence, and B-cell reconstitution were assessed. Pretreatment tumor biopsies from five patients with divergent outcomes underwent spatial single-cell transcriptomic profiling.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n 32 patients were treated, including 24 with diffuse large B-cell lymphoma. Among 31 evaluable patients, the best overall response rate was 74%, including 58% achieving complete remission. Median progression-free and overall survival were 6.8 and 22.1 months, respectively. Response rates were higher in patients with normal lactate dehydrogenase. CAR-T expansion peaked on days 7\u201317, and persistence exceeded 500 days in long-term responders. Cytokine release syndrome occurred in 53% (12% grade \u22653) and immune effector cell-associated neurotoxicity syndrome in 9% (all grade 3), with no lasting deficits. Spatial profiling identified two dominant tumor architectures: (1) a B-cell-dominant phenotype, in which durable remission was associated with heightened apoptotic competence in malignant B cells, and (2) a fibroblast-enriched and monocyte\/macrophage-enriched phenotype, in which response correlated with a chemokine-rich, T-cell-permissive microenvironment.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Bispecific CD19\/20 CAR-T therapy produced durable clinical activity with manageable toxicity. Spatial single-cell analysis reveals distinct tumor-intrinsic and microenvironmental features associated with CAR-T responsiveness, providing a spatially informed framework for understanding heterogeneous therapeutic outcomes.<\/jats:p>\n <\/jats:sec>\n \n Trial registration number<\/jats:title>\n \n NCT04723914<\/jats:ext-link>\n .\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1136\/jitc-2026-015114","type":"journal-article","created":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T17:05:26Z","timestamp":1779037526000},"page":"e015114","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Clinical outcomes and spatial transcriptomic profiles of CD19\/20 CAR-T therapy in relapsed or refractory B-cell non-Hodgkin\u2019s lymphoma"],"prefix":"10.1136","volume":"14","clinical-trial-number":[{"clinical-trial-number":"nct04723914","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04723914","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04723914","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Lixin","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Hematology and Oncology, Shenzhen University General Hospital, International Cancer Center, Hematology Institution, Haoshi Cell Therapy Institute of Shenzhen University, Shenzhen University Medical School, Shenzhen University, Shenzhen, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8381-1823","authenticated-orcid":false,"given":"Chuling","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Shenzhen University General Hospital, International Cancer Center, Hematology 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