{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T11:38:23Z","timestamp":1791805103925,"version":"4.3.4"},"reference-count":10,"publisher":"BMJ","issue":"9","license":[{"start":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T00:00:00Z","timestamp":1758585600000},"content-version":"unspecified","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"AGAUR Generalitat de Catalunya","award":["2021-SGR-01162"],"award-info":[{"award-number":["2021-SGR-01162"]}]},{"DOI":"10.13039\/501100002704","name":"Fundaci\u00f3n Cient\u00edfica Asociaci\u00f3n Espa\u00f1ola Contra el C\u00e1ncer","doi-asserted-by":"publisher","award":["ATTRA236784"],"award-info":[{"award-number":["ATTRA236784"]}],"id":[{"id":"10.13039\/501100002704","id-type":"DOI","asserted-by":"publisher"}]},{"name":"RICORS-TERAV+","award":["RD24\/0014\/0001"],"award-info":[{"award-number":["RD24\/0014\/0001"]}]},{"name":"\"la Caixa\u201d Foundation","award":["LCF\/PR\/SP23\/52950004"],"award-info":[{"award-number":["LCF\/PR\/SP23\/52950004"]}]},{"name":"Instituto de Salud Carlos III, Ministerio de Sanidad, Fondo Europeo de Desarrollo Regional (FEDER) \u201cuna manera de hacer Europa\u201d","award":["PI18\/00775"],"award-info":[{"award-number":["PI18\/00775"]}]},{"name":"Instituto de Salud Carlos III, Ministerio de Sanidad, Fondo Europeo de Desarrollo Regional (FEDER) \u201cuna manera de hacer Europa\u201d","award":["PICI18\/00012"],"award-info":[{"award-number":["PICI18\/00012"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2025,8,25]]},"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:p>\n                    Patients with B-cell malignancies receiving CD19-targeted chimeric antigen receptor (CAR) T-cell therapy may experience treatment failure due to various mechanisms. One significant factor is the host\u2019s immune response against the CAR-T product, mainly triggered by the immunogenicity of non-human sequences present in the CAR construct. In the CART19-BE-01 clinical trial (\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT03144583\">NCT03144583<\/jats:ext-link>\n                    , ClinicalTrials.gov), patients with relapsed\/refractory B-cell malignancies received treatment with varnimcabtagene autoleucel (ARI-0001 cells), a CD19-targeted autologous CAR-T product. During follow-up, both humoral and cellular immune responses were assessed against the extracellular domain of ARI-0001 cells, which was derived from the murine monoclonal antibody A3B1. Here, we report the case of a patient with B-cell acute lymphoblastic leukemia who required two infusions of ARI-0001 cells. Between the first and second CAR-T19 infusions, human antimurine antibodies were detected, which in vitro diminished the cytotoxicity of ARI-0001 cells against the CD19-positive NALM6 cell line. Furthermore, CD4\n                    <jats:sup>+<\/jats:sup>\n                    specific T cells against the CAR19 construct were isolated from the patient\u2019s peripheral blood mononuclear cells, showing recognition of the murine single-chain variable fragment peptides presented by human leukocyte antigen class II. This case underscores the need to monitor immune responses in patients before considering subsequent CAR-T infusions to preserve treatment efficacy.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Trial registration number<\/jats:bold>\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT03144583\">NCT03144583<\/jats:ext-link>\n                    .\n                  <\/jats:p>","DOI":"10.1136\/jitc-2024-010792","type":"journal-article","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T04:55:28Z","timestamp":1758603328000},"page":"e010792","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["T-cell responses against CD19-targeted CAR T cells varnimcabtagene autoleucel (ARI-0001): implications for immune response and therapy outcomes"],"prefix":"10.1136","volume":"13","clinical-trial-number":[{"clinical-trial-number":"nct03144583","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03144583","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Ariadna","family":"Bartol\u00f3-Ibars","sequence":"first","affiliation":[{"name":"Joint Platform of Immunotherapy Hospital Sant Joan de D\u00e9u (HSJD)-Hospital Cl\u00ednic of Barcelona (HCB), Barcelona, Spain"},{"name":"Fundaci\u00f3 de Recerca Cl\u00ednic Barcelona - IDIBAPS, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Aran","sequence":"additional","affiliation":[{"name":"Joint Platform of Immunotherapy Hospital Sant Joan de D\u00e9u (HSJD)-Hospital Cl\u00ednic of Barcelona (HCB), Barcelona, Spain"},{"name":"Fundaci\u00f3 de Recerca Cl\u00ednic Barcelona - IDIBAPS, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4779-4648","authenticated-orcid":false,"given":"Alexandra M","family":"Johansson","sequence":"additional","affiliation":[{"name":"Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4699-6862","authenticated-orcid":false,"given":"Valent\u00edn","family":"Ortiz-Maldonado","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3 de Recerca Cl\u00ednic Barcelona - IDIBAPS, Barcelona, Spain"},{"name":"Department of Hematology, Hospital Cl\u00ednic de Barcelona, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nela","family":"Klein-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Joint Platform of Immunotherapy Hospital Sant Joan de D\u00e9u (HSJD)-Hospital Cl\u00ednic of Barcelona (HCB), Barcelona, Spain"},{"name":"Fundaci\u00f3 de Recerca Cl\u00ednic Barcelona - IDIBAPS, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Alonso-Saladrigues","sequence":"additional","affiliation":[{"name":"Leukemia and Lymphoma Department, Pediatric Cancer Center Barcelona HSJD, Barcelona, Spain"},{"name":"Institut de Recerca Sant Joan de D\u00e9u, Barcelona, Spain"},{"name":"University of Barcelona, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7217-5729","authenticated-orcid":false,"given":"Eddie","family":"James","sequence":"additional","affiliation":[{"name":"Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alvaro","family":"Urbano-Ispizua","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3 de Recerca Cl\u00ednic Barcelona - IDIBAPS, Barcelona, Spain"},{"name":"Department of Hematology, Hospital Cl\u00ednic de Barcelona, Barcelona, Spain"},{"name":"Department of Medicine, University of Barcelona, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susana","family":"Rives","sequence":"additional","affiliation":[{"name":"Leukemia and Lymphoma Department, Sant Joan de Deu Hospital, Barcelona, Spain"},{"name":"Sant Joan de Deu Research Institute, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5157-4376","authenticated-orcid":false,"given":"Julio","family":"Delgado","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3 de Recerca Cl\u00ednic Barcelona - IDIBAPS, Barcelona, Spain"},{"name":"Department of Hematology, Hospital Cl\u00ednic de Barcelona, Barcelona, Spain"},{"name":"University of Barcelona, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Europa Azucena","family":"Gonz\u00e1lez-Navarro","sequence":"additional","affiliation":[{"name":"Joint Platform of Immunotherapy Hospital Sant Joan de D\u00e9u (HSJD)-Hospital Cl\u00ednic of Barcelona (HCB), Barcelona, Spain"},{"name":"Fundaci\u00f3 de Recerca Cl\u00ednic Barcelona - IDIBAPS, Barcelona, Spain"},{"name":"Department of Immunology, HCB, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William W","family":"Kwok","sequence":"additional","affiliation":[{"name":"Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3064-1648","authenticated-orcid":false,"given":"Manel","family":"Juan","sequence":"additional","affiliation":[{"name":"Joint Platform of Immunotherapy Hospital Sant Joan de D\u00e9u (HSJD)-Hospital Cl\u00ednic of Barcelona (HCB), Barcelona, Spain"},{"name":"Fundaci\u00f3 de Recerca Cl\u00ednic Barcelona - IDIBAPS, Barcelona, Spain"},{"name":"University of Barcelona, Barcelona, Spain"},{"name":"Department of Immunology, HCB, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2025,9,22]]},"reference":[{"key":"2026052108452328000_13.9.e010792.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0564-6"},{"key":"2026052108452328000_13.9.e010792.2","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2022.886546","article-title":"Immunogenicity of CAR-T Cell Therapeutics: Evidence, Mechanism and Mitigation","volume":"13","author":"Khan","year":"2022","journal-title":"Front Immunol"},{"key":"2026052108452328000_13.9.e010792.3","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.omtm.2018.11.010","article-title":"Development of a Novel Anti-CD19 Chimeric Antigen Receptor: A Paradigm for an Affordable CAR T Cell Production at Academic Institutions","volume":"12","author":"Castella","year":"2019","journal-title":"Mol Ther Methods Clin Dev"},{"key":"2026052108452328000_13.9.e010792.4","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1016\/j.ymthe.2020.09.027","article-title":"CART19-BE-01: A Multicenter Trial of ARI-0001 Cell Therapy in Patients with CD19+ Relapsed\/Refractory Malignancies","volume":"29","author":"Ort\u00edz-Maldonado","year":"2021","journal-title":"Mol Ther"},{"key":"2026052108452328000_13.9.e010792.5","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-021-00476-2"},{"key":"2026052108452328000_13.9.e010792.6","doi-asserted-by":"publisher","DOI":"10.1007\/s40259-019-00354-5"},{"key":"2026052108452328000_13.9.e010792.7","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa379"},{"key":"2026052108452328000_13.9.e010792.8","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1038\/icb.1990.50","article-title":"Development of human anti-murine antibody (HAMA) response in patients","volume":"68 (Pt 6)","author":"Tjandra","year":"1990","journal-title":"Immunol Cell Biol"},{"key":"2026052108452328000_13.9.e010792.9","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-022-01572-7"},{"key":"2026052108452328000_13.9.e010792.10","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2021-002758","article-title":"Activation of GM-CSF and TLR2 signaling synergistically enhances antigen-specific antitumor immunity and modulates the tumor microenvironment","volume":"9","author":"Yan","year":"2021","journal-title":"J Immunother Cancer"}],"container-title":["Journal for ImmunoTherapy of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jitc-2024-010792","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T15:45:35Z","timestamp":1779378335000},"score":1,"resource":{"primary":{"URL":"https:\/\/jitc.bmj.com\/lookup\/doi\/10.1136\/jitc-2024-010792"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9]]},"references-count":10,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9,22]]},"published-print":{"date-parts":[[2025,9]]}},"alternative-id":["10.1136\/jitc-2024-010792"],"URL":"https:\/\/doi.org\/10.1136\/jitc-2024-010792","relation":{},"ISSN":["2051-1426"],"issn-type":[{"value":"2051-1426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9]]}}}