{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T00:47:24Z","timestamp":1794271644151,"version":"4.9.0"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2024,4,26]],"date-time":"2024-04-26T00:00:00Z","timestamp":1714089600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2024,4,26]],"date-time":"2024-04-26T00:00:00Z","timestamp":1714089600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Med"],"published-print":{"date-parts":[[2024,6]]},"DOI":"10.1038\/s41591-024-02964-1","type":"journal-article","created":{"date-parts":[[2024,4,26]],"date-time":"2024-04-26T06:03:04Z","timestamp":1714111384000},"page":"1593-1601","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":203,"title":["Bispecific T cell engager therapy for refractory rheumatoid arthritis"],"prefix":"10.1038","volume":"30","author":[{"given":"Laura","family":"Bucci","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Hagen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Rothe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Gabriella","family":"Raimondo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo","family":"Fagni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Tur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Wirsching","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen","family":"Wacker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Artur","family":"Wilhelm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Philippe","family":"Auger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3729-9566","authenticated-orcid":false,"given":"Milena","family":"Pachowsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5418-3349","authenticated-orcid":false,"given":"Markus","family":"Eckstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7383-4212","authenticated-orcid":false,"given":"Stefano","family":"Alivernini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Zoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerhard","family":"Kr\u00f6nke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Uderhardt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aline","family":"Bozec","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5347-0060","authenticated-orcid":false,"given":"Maria-Antonietta","family":"D\u2019Agostino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8740-9615","authenticated-orcid":false,"given":"Georg","family":"Schett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2873-5135","authenticated-orcid":false,"given":"Ricardo","family":"Grieshaber-Bouyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,4,26]]},"reference":[{"key":"2964_CR1","doi-asserted-by":"publisher","first-page":"2205","DOI":"10.1056\/NEJMra1004965","volume":"365","author":"IB McInnes","year":"2011","unstructured":"McInnes, I. B. & Schett, G. The pathogenesis of rheumatoid arthritis. N. Engl. J. Med. 365, 2205\u20132219 (2011).","journal-title":"N. Engl. J. Med."},{"key":"2964_CR2","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1056\/NEJMra2103726","volume":"388","author":"EM Gravallese","year":"2023","unstructured":"Gravallese, E. M. & Firestein, G. S. Rheumatoid arthritis\u2014common origins, divergent mechanisms. N. Engl. J. Med. 388, 529\u2013542 (2023).","journal-title":"N. Engl. J. Med."},{"key":"2964_CR3","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1038\/nri.2016.124","volume":"17","author":"V Malmstr\u00f6m","year":"2016","unstructured":"Malmstr\u00f6m, V., Catrina, A. I. & Klareskog, L. The immunopathogenesis of seropositive rheumatoid arthritis: from triggering to targeting. Nat. Rev. Immunol. 17, 60\u201375 (2016).","journal-title":"Nat. Rev. Immunol."},{"key":"2964_CR4","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1371\/journal.pmed.0060001","volume":"6","author":"F Humby","year":"2009","unstructured":"Humby, F. et al. Ectopic lymphoid structures support ongoing production of class-switched autoantibodies in rheumatoid synovium. PLoS Med. 6, 59\u201375 (2009).","journal-title":"PLoS Med."},{"key":"2964_CR5","doi-asserted-by":"publisher","first-page":"2572","DOI":"10.1056\/NEJMoa032534","volume":"350","author":"JC Edwards","year":"2004","unstructured":"Edwards, J. C. et al. Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N. Engl. J. Med. 350, 2572\u20132581 (2004).","journal-title":"N. Engl. J. Med."},{"key":"2964_CR6","doi-asserted-by":"publisher","first-page":"966","DOI":"10.1136\/annrheumdis-2017-212862","volume":"77","author":"MH Buch","year":"2018","unstructured":"Buch, M. H. Defining refractory rheumatoid arthritis. Ann. Rheum. Dis. 77, 966\u2013969 (2018).","journal-title":"Ann. Rheum. Dis."},{"key":"2964_CR7","doi-asserted-by":"publisher","first-page":"1256","DOI":"10.1038\/s41591-022-01789-0","volume":"28","author":"F Rivellese","year":"2022","unstructured":"Rivellese, F. et al. Rituximab versus tocilizumab in rheumatoid arthritis: synovial biopsy-based biomarker analysis of the phase 4 R4RA randomized trial. Nat. Med. 28, 1256\u20131268 (2022).","journal-title":"Nat. Med."},{"key":"2964_CR8","doi-asserted-by":"publisher","first-page":"1907","DOI":"10.1056\/NEJMoa035075","volume":"349","author":"JM Kremer","year":"2003","unstructured":"Kremer, J. M. et al. Treatment of rheumatoid arthritis by selective inhibition of T-cell activation with fusion protein CTLA4Ig. N. Engl. J. Med. 349, 1907\u20131915 (2003).","journal-title":"N. Engl. J. Med."},{"key":"2964_CR9","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1038\/s41571-020-0347-5","volume":"17","author":"ME Goebeler","year":"2020","unstructured":"Goebeler, M. E. & Bargou, R. C. T cell-engaging therapies\u2014BiTEs and beyond. Nat. Rev. Clin. Oncol. 17, 418\u2013434 (2020).","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"2964_CR10","doi-asserted-by":"publisher","first-page":"836","DOI":"10.1056\/NEJMoa1609783","volume":"376","author":"H Kantarjian","year":"2017","unstructured":"Kantarjian, H. et al. Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. N. Engl. J. Med. 376, 836\u2013847 (2017).","journal-title":"N. Engl. J. Med."},{"key":"2964_CR11","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1007\/s00262-003-0496-2","volume":"53","author":"M Gruen","year":"2004","unstructured":"Gruen, M., Bommert, K. & Bargou, R. C. T-cell-mediated lysis of B cells induced by a CD19\u00d7CD3 bispecific single-chain antibody is perforin dependent and death receptor independent. Cancer Immunol. Immunother. 53, 625\u2013632 (2004).","journal-title":"Cancer Immunol. Immunother."},{"key":"2964_CR12","doi-asserted-by":"publisher","first-page":"2098","DOI":"10.1182\/blood.V95.6.2098","volume":"95","author":"A Loffler","year":"2000","unstructured":"Loffler, A. et al. A recombinant bispecific single-chain antibody, CD19\u00d7CD3, induces rapid and high lymphoma-directed cytotoxicity by unstimulated T lymphocytes. Blood 95, 2098\u20132103 (2000).","journal-title":"Blood"},{"key":"2964_CR13","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1002\/ijc.20908","volume":"115","author":"P Hoffmann","year":"2005","unstructured":"Hoffmann, P. et al. Serial killing of tumor cells by cytotoxic T cells redirected with a CD19-\/CD3-bispecific single-chain antibody construct. Int J. Cancer 115, 98\u2013104 (2005).","journal-title":"Int J. Cancer"},{"key":"2964_CR14","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1016\/j.molimm.2005.03.007","volume":"43","author":"S Offner","year":"2006","unstructured":"Offner, S., Hofmeister, R., Romaniuk, A., Kufer, P. & Baeuerle, P. A. Induction of regular cytolytic T cell synapses by bispecific single-chain antibody constructs on MHC class I-negative tumor cells. Mol. Immunol. 43, 763\u2013771 (2006).","journal-title":"Mol. Immunol."},{"key":"2964_CR15","doi-asserted-by":"publisher","first-page":"974","DOI":"10.1126\/science.1158545","volume":"321","author":"R Bargou","year":"2008","unstructured":"Bargou, R. et al. Tumor regression in cancer patients by very low doses of a T cell-engaging antibody. Science 321, 974\u2013977 (2008).","journal-title":"Science"},{"key":"2964_CR16","doi-asserted-by":"publisher","first-page":"2493","DOI":"10.1200\/JCO.2010.32.7270","volume":"29","author":"MS Topp","year":"2011","unstructured":"Topp, M. S. et al. Targeted therapy with the T-cell-engaging antibody blinatumomab of chemotherapy-refractory minimal residual disease in B-lineage acute lymphoblastic leukemia patients results in high response rate and prolonged leukemia-free survival. J. Clin. Oncol. 29, 2493\u20132498 (2011).","journal-title":"J. Clin. Oncol."},{"key":"2964_CR17","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1002\/art.22400","volume":"56","author":"K Vos","year":"2007","unstructured":"Vos, K. et al. Early effects of rituximab on the synovial cell infiltrate in patients with rheumatoid arthritis. Arthritis Rheum. 56, 772\u2013778 (2007).","journal-title":"Arthritis Rheum."},{"key":"2964_CR18","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1038\/s41584-020-00543-5","volume":"17","author":"G Schett","year":"2021","unstructured":"Schett, G., Tanaka, Y. & Isaacs, J. D. Why remission is not enough: underlying disease mechanisms in RA that prevent cure. Nat. Rev. Rheumatol. 17, 135\u2013144 (2021).","journal-title":"Nat. Rev. Rheumatol."},{"key":"2964_CR19","doi-asserted-by":"publisher","first-page":"1114","DOI":"10.1056\/NEJMoa050524","volume":"353","author":"MC Genovese","year":"2005","unstructured":"Genovese, M. C. et al. Abatacept for rheumatoid arthritis refractory to tumor necrosis factor alpha inhibition. N. Engl. J. Med. 353, 1114\u20131123 (2005).","journal-title":"N. Engl. J. Med."},{"key":"2964_CR20","doi-asserted-by":"publisher","first-page":"980","DOI":"10.1093\/rheumatology\/kel453","volume":"46","author":"RN Jois","year":"2007","unstructured":"Jois, R. N., Masding, A., Somerville, M., Gaffney, K. & Scott, D. G. Rituximab therapy in patients with resistant rheumatoid arthritis: real-life experience. Rheumatol. (Oxf.) 46, 980\u2013982 (2007).","journal-title":"Rheumatol. (Oxf.)"},{"key":"2964_CR21","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1056\/NEJMc2107725","volume":"385","author":"D Mougiakakos","year":"2021","unstructured":"Mougiakakos, D. et al. CD19-targeted CAR T cells in refractory systemic lupus erythematosus. N. Engl. J. Med. 385, 567\u2013569 (2021).","journal-title":"N. Engl. J. Med."},{"key":"2964_CR22","doi-asserted-by":"publisher","first-page":"2124","DOI":"10.1038\/s41591-022-02017-5","volume":"28","author":"A Mackensen","year":"2022","unstructured":"Mackensen, A. et al. Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus. Nat. Med. 28, 2124\u20132132 (2022).","journal-title":"Nat. Med."},{"key":"2964_CR23","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.1136\/ard-2023-223952","volume":"82","author":"C Bergmann","year":"2023","unstructured":"Bergmann, C. et al. Treatment of a patient with severe systemic sclerosis (SSc) using CD19-targeted CAR T cells. Ann. Rheum. Dis. 82, 1117\u20131120 (2023).","journal-title":"Ann. Rheum. Dis."},{"key":"2964_CR24","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1016\/S0140-6736(23)00023-5","volume":"401","author":"F Muller","year":"2023","unstructured":"Muller, F. et al. CD19-targeted CAR T cells in refractory antisynthetase syndrome. Lancet 401, 815\u2013818 (2023).","journal-title":"Lancet"},{"key":"2964_CR25","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1056\/NEJMoa2308917","volume":"390","author":"F Muller","year":"2024","unstructured":"Muller, F. et al. CD19 CAR T-cell therapy in autoimmune disease - a case series with follow-up. N. Engl. J. Med. 390, 687\u2013700 (2024).","journal-title":"N. Engl. J. Med."},{"key":"2964_CR26","doi-asserted-by":"publisher","first-page":"1157","DOI":"10.1016\/S0140-6736(21)00889-8","volume":"398","author":"M Hutchings","year":"2021","unstructured":"Hutchings, M. et al. Dose escalation of subcutaneous epcoritamab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: an open-label, phase 1\/2 study. Lancet 398, 1157\u20131169 (2021).","journal-title":"Lancet"},{"key":"2964_CR27","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1056\/NEJMoa2203478","volume":"387","author":"P Moreau","year":"2022","unstructured":"Moreau, P. et al. Teclistamab in relapsed or refractory multiple myeloma. N. Engl. J. Med. 387, 495\u2013505 (2022).","journal-title":"N. Engl. J. Med."},{"key":"2964_CR28","doi-asserted-by":"publisher","first-page":"2259","DOI":"10.1038\/s41591-023-02528-9","volume":"29","author":"AM Lesokhin","year":"2023","unstructured":"Lesokhin, A. M. et al. Elranatamab in relapsed or refractory multiple myeloma: phase 2 MagnetisMM-3 trial results. Nat. Med. 29, 2259\u20132267 (2023).","journal-title":"Nat. Med."},{"key":"2964_CR29","doi-asserted-by":"crossref","unstructured":"Taubmann, J. et al. Chimeric antigen receptor T cell treatment: unraveling the role of B cells in systemic lupus erythematosus. Arthritis Rheumatol. 76, 497\u2013504 (2024).","DOI":"10.1002\/art.42784"},{"key":"2964_CR30","doi-asserted-by":"publisher","first-page":"5154","DOI":"10.1182\/blood-2013-02-485623","volume":"121","author":"DT Teachey","year":"2013","unstructured":"Teachey, D. T. et al. Cytokine release syndrome after blinatumomab treatment related to abnormal macrophage activation and ameliorated with cytokine-directed therapy. Blood 121, 5154\u20135157 (2013).","journal-title":"Blood"},{"key":"2964_CR31","doi-asserted-by":"publisher","first-page":"1580","DOI":"10.1136\/ard.2010.138461","volume":"69","author":"D Aletaha","year":"2010","unstructured":"Aletaha, D. et al. 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology\/European League Against Rheumatism collaborative initiative. Ann. Rheum. Dis. 69, 1580\u20131588 (2010).","journal-title":"Ann. Rheum. Dis."},{"key":"2964_CR32","doi-asserted-by":"publisher","first-page":"954","DOI":"10.1136\/ard.2007.084459","volume":"68","author":"G Wells","year":"2009","unstructured":"Wells, G. et al. Validation of the 28-joint Disease Activity Score (DAS28) and European League Against Rheumatism response criteria based on C-reactive protein against disease progression in patients with rheumatoid arthritis, and comparison with the DAS28 based on erythrocyte sedimentation rate. Ann. Rheum. Dis. 68, 954\u2013960 (2009).","journal-title":"Ann. Rheum. Dis."},{"key":"2964_CR33","doi-asserted-by":"publisher","first-page":"e000428","DOI":"10.1136\/rmdopen-2016-000428","volume":"3","author":"MA D\u2019Agostino","year":"2017","unstructured":"D\u2019Agostino, M. A. et al. Scoring ultrasound synovitis in rheumatoid arthritis: a EULAR-OMERACT ultrasound taskforce-Part 1: definition and development of a standardised, consensus-based scoring system. RMD Open 3, e000428 (2017).","journal-title":"RMD Open"},{"key":"2964_CR34","doi-asserted-by":"publisher","first-page":"1136","DOI":"10.2967\/jnumed.122.263922","volume":"63","author":"T Kuwert","year":"2022","unstructured":"Kuwert, T., Schmidkonz, C., Prante, O., Schett, G. & Ramming, A. FAPI PET opens a new window to understanding immune-mediated inflammatory diseases. J. Nucl. Med. 63, 1136\u20131137 (2022).","journal-title":"J. Nucl. Med."},{"key":"2964_CR35","doi-asserted-by":"publisher","first-page":"1601","DOI":"10.1002\/art.41726","volume":"73","author":"S Alivernini","year":"2021","unstructured":"Alivernini, S. et al. Inclusion of synovial tissue-derived characteristics in a nomogram for the prediction of treatment response in treatment-naive rheumatoid arthritis patients. Arthritis Rheumatol. 73, 1601\u20131613 (2021).","journal-title":"Arthritis Rheumatol."},{"key":"2964_CR36","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1111\/j.1365-2559.2006.02508.x","volume":"49","author":"V Krenn","year":"2006","unstructured":"Krenn, V. et al. Synovitis score: discrimination between chronic low-grade and high-grade synovitis. Histopathology 49, 358\u2013364 (2006).","journal-title":"Histopathology"}],"container-title":["Nature Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41591-024-02964-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41591-024-02964-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41591-024-02964-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,19]],"date-time":"2024-06-19T10:10:57Z","timestamp":1718791857000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41591-024-02964-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,26]]},"references-count":36,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2024,6]]}},"alternative-id":["2964"],"URL":"https:\/\/doi.org\/10.1038\/s41591-024-02964-1","relation":{},"ISSN":["1078-8956","1546-170X"],"issn-type":[{"value":"1078-8956","type":"print"},{"value":"1546-170X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,26]]},"assertion":[{"value":"13 December 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 April 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 April 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"There are no conflicts of interest related to this study. The study received no commercial funding. M.-A.D.\u2019A. has received speaker honoraria from Abbvie, Novartis and Janssen, which were not related to this study. G.S. has received speaker honoraria from Janssen and Novartis, which were not related to this study. The other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}