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Here we report on treatment under compassionate use with the CD19\u00d7CD3 T cell engager (TCE) blinatumomab and the BCMA\u00d7CD3 TCE teclistamab in five patients with treatment-refractory ASyS and in five patients with treatment-refractory SSc, respectively. Induction therapy with blinatumomab or teclistamab reduced target cells in affected muscle and skin, respectively, and decreased autoantibody titers. Blinatumomab induced rapid clinical, serological and histological improvement of myositis and stabilization of interstitial lung disease (ILD) in patients with ASyS. Teclistamab improved skin fibrosis, stabilized ILD and resolved tendon friction rubs in patients with SSc. Inhibition of B cell redifferentiation by maintenance therapy with rituximab (RTX) enabled prolonged disease control, even for patients previously unresponsive to RTX. Treatment was associated with adverse events including cytokine release syndrome (CRS) up to grade 3, in two patients with ASyS and in all patients with SSc. No immune effector cell-associated neurotoxicity syndrome (ICANS) occurred. Respiratory infections treated with antibiotics occurred in six patients. Blinatumomab and teclistamab may offer potential as rescue therapies for patients with treatment-refractory ASyS and SSc.<\/jats:p>","DOI":"10.1038\/s41591-026-04238-4","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T10:02:53Z","timestamp":1771495373000},"page":"1530-1542","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Bispecific T cell engagers for treatment-refractory autoimmune connective tissue diseases"],"prefix":"10.1038","volume":"32","author":[{"given":"Christina","family":"D\u00fcsing","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea-Hermina","family":"Gy\u00f6rfi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9123-4044","authenticated-orcid":false,"given":"Ayla 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J.H.W.D. has received grants or holds contracts from AbbVie, Anamar, Argenx, ARXX, Bristol Myers Squibb, Bayer Pharma, Boehringer Ingelheim, Cantargia, Celgene, CSL Behring, ExoTherapeutics, Galapagos, GlaxoSmithKline, Inventiva, Kiniksa, Lassen, Novartis, Sanofi-Aventis, RedX and UCB; consulting fees from AbbVie, Active Biotech, Anamar, ARXX, AstraZeneca, Bayer Pharma, Boehringer Ingelheim, Celgene, Galapagos, Genentech, GlaxoSmithKline, Inventiva, Janssen, Novartis, Pfizer, Roche and UCB; payment or honoraria for lectures, presentations, speaker\u02bcs bureaus, manuscript writing or educational events from AbbVie, Active Biotech, Anamar, ARXX, AstraZeneca, Bayer Pharma, Boehringer Ingelheim, Celgene, Galapagos, Genentech, GlaxoSmithKline, Inventiva, Janssen, Novartis, Pfizer, Roche and UCB; payment for expert testimony from AbbVie, Anamar, ARXX, AstraZeneca, Bayer Pharma, Boehringer Ingelheim, Cantargia, Celgene, Galapagos, Genentech, GlaxoSmithKline, Inventiva, Janssen, Novartis, Pfizer, Roche and UCB; support for attending meetings and\/or travel from AbbVie and SOBI; stock or stock options from 4D Science and FibroCure; and receipt of equipment, materials, drugs, medical writing, gifts or other services from Boehringer Ingelheim. A.-H.G. has received honoraria for presentations from Boehringer Ingelheim and AbbVie. T.R. received honoraria for lecturing, consulting, travel expenses for attending meetings and research support from Alexion, ArgenX, Amgen, Johnson & Johnson, Merck, Novartis, Roche, Sanofi and UCB. C.D. received honoraria for lecturing, consulting and travel expenses for attending meetings from Novartis, GlaxoSmithKline, Medac, AstraZeneca, AlfaSigma, Johnson & Johnson, Sanofi, Lilly, Amgen, AbbVie, Kyverna, Pfizer and Deutsche Rheuma-Liga. M.H. received speaker\u2019s fees and travel support from Century Therapeutics, AstraZeneca, Boehringer Ingelheim, Johnson & Johnson, Lilly, Bristol Myers Squibb, Kyverna, UCB, Sanofi, AlfaSigma, Gilead, Pfizer and AbbVie. G.S. received speaker\u2019s honoraria from Bristol Myers Squibb, Cabaletta, Janssen, Kyverna, Novartis and UCB. R.G.-B. has received research support from Kyverna and speaker\u02bcs honoraria from Bristol Myers Squibb, Kyverna and Novartis. C.P.H. received consulting fees from Schering-Plough, Pfizer, Basilea, Boehringer Ingelheim, Novartis, Roche, Astellas, Gilead, Merck Sharp & Dohme, Lilly, Intermune, Fresenius and Voiant; research funding from Siemens, Pfizer, MeVis, Boehringer Ingelheim and Exscientia; and lecture fees from Gilead, Essex, Schering-Plough, AstraZeneca, Lilly, Roche, Merck Sharp & Dohme, Pfizer, Bracco, MEDA Pharma, Intermune, Chiesi, Siemens, Covidien, Pierre Fabre, Boehringer Ingelheim, Grifols, Novartis, Basilea, Bayer and Sanofi. He also has stock ownership in GlaxoSmithKline and a patent titled \u2018Method and device for representing the microstructure of the lungs\u2019 (IPC8 class: AA61B5055FI, PAN: 20080208038, inventors: Schreiber, W., Wolf, U., Scholz, A. W. & Heussel, C. P.). The other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}