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Bispecific T cell engagers for treatment-refractory autoimmune connective tissue diseases

Autoimmune-mediated connective tissue diseases such as antisynthetase syndrome (ASyS) and systemic sclerosis (SSc) have a high unmet medical need. Here we report on treatment under compassionate use with the CD19×CD3 T cell engager (TCE) blinatumomab and the BCMA×CD3 TCE teclistamab in five patients...

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Main Authors: Düsing, Christina (Author) , Györfi, Andrea-Hermina (Author) , Stütz, Ayla Nadja (Author) , Lahu, Laura-Marie (Author) , Deicher, Franca Sophie (Author) , Li, Yi-Nan (Author) , Bruch, Peter-Martin (Author) , Matei, Alexandru-Emil (Author) , Micu, Alexandru (Author) , Filla, Tim (Author) , Koziel, Sarah (Author) , Hölscher, Alexander Sebastian (Author) , Röhrich, Manuel (Author) , Lorenz, Hanns-Martin (Author) , Cramer, Mareike (Author) , Antoch, Gerald (Author) , Timm, Jörg (Author) , Abusabha, Yousef (Author) , Ruck, Tobias (Author) , Homey, Bernhard (Author) , Kreuter, Alexander (Author) , Buehring, Björn (Author) , Radujkovic, Aleksandar (Author) , Heußel, Claus Peter (Author) , Hagen, Melanie (Author) , Grieshaber-Bouyer, Ricardo (Author) , Schett, Georg (Author) , Brunn, Anna (Author) , Dietrich, Sascha (Author) , Merkt, Wolfgang (Author) , Distler, Jörg H. W. (Author)
Format: Article (Journal)
Language:English
Published: 19 February 2026
In: Nature medicine
Year: 2026, Pages: 1-35
ISSN:1546-170X
DOI:10.1038/s41591-026-04238-4
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41591-026-04238-4
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41591-026-04238-4
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Author Notes:Christina Düsing, Andrea-Hermina Györfi, Ayla Nadja Stütz, Laura-Marie Lahu, Franca Sophie Deicher, Yi-Nan Li, Peter-Martin Bruch, Alexandru-Emil Matei, Alexandru Micu, Tim Filla, Sarah Koziel, Alexander Sebastian Hölscher, Manuel Röhrich, Hanns-Martin Lorenz, Mareike Cramer, Gerald Antoch, Jörg Timm, Yousef Abusabha, Tobias Ruck, Bernhard Homey, Alexander Kreuter, Björn Buehring, Aleksandar Radujkovic, Claus Peter Heußel, Melanie Hagen, Ricardo Grieshaber-Bouyer, Georg Schett, Anna Brunn, Sascha Dietrich, Wolfgang Merkt & Jörg H.W. Distler
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Summary:Autoimmune-mediated connective tissue diseases such as antisynthetase syndrome (ASyS) and systemic sclerosis (SSc) have a high unmet medical need. Here we report on treatment under compassionate use with the CD19×CD3 T cell engager (TCE) blinatumomab and the BCMA×CD3 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.
Item Description:Online veröffentlicht: 19. Februar 2026
Gesehen am 14.04.2026
Physical Description:Online Resource
ISSN:1546-170X
DOI:10.1038/s41591-026-04238-4

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