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 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.
Authors
- Yousef Abusabha
- Y. LI
- Christina Düsing (ORCID: https://orcid.org/0009-0005-2601-8203)
- Ayla Nadja Stütz
- Aleksandar Radujkovic (ORCID: https://orcid.org/0000-0002-8543-5016)
- Wolfgang Merkt (ORCID: https://orcid.org/0000-0002-3108-154X)
- Claus Peter Heußel (ORCID: https://orcid.org/0000-0001-5809-5733)
- Manuel Röhrich (ORCID: https://orcid.org/0000-0001-7609-243X)
- Sascha Dietrich
- Alexander Kreuter (ORCID: https://orcid.org/0000-0003-2275-499X)
- Tim Filla (ORCID: https://orcid.org/0000-0001-5628-8398)
- Franca Sophie Deicher
- Sarah Koziel (ORCID: https://orcid.org/0009-0003-8002-5127)
- L. Núñez
- Hanns-Martin Lorenz
- A. Micu
- A. Brunn
- Laura-Marie Lahu
- Ricardo Grieshaber-Bouyer
- Tobias Ruck
- Melanie Hagen
- Peter-Martin Bruch
- J Timm
- Alexandru-Emil Matei
- Björn Buehring
- Mareike Cramer
- Jörg H. W. Distler
- Georg Schett
- Alexander Sebastian Hölscher
Institutions
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- Johannes Gutenberg University Mainz (DE)
- Heidelberg University (DE)
- University Hospital Heidelberg (DE)
- Universitätsklinikum Erlangen (DE)
- Düsseldorf University Hospital (DE)
- Fraunhofer Institute for Translational Medicine and Pharmacology (DE)
- Klinik und Poliklinik für Psychosomatische Medizin und Psychotherapie (DE)
- Helios Universitätsklinikum Wuppertal (DE)
- HELIOS St. Elisabeth Klinik Oberhausen (DE)
- German Center for Lung Research (DE)
- BG Klinikum Duisburg (DE)
- BG University Hospital Bergmannsheil Bochum (DE)
- Heinrich Heine University Düsseldorf (DE)
Publication Details
- Journal
- Nature Medicine
- Published
- 2026-02-19
- DOI
- https://doi.org/10.1038/s41591-026-04238-4
- Primary Topic
- Inflammatory Myopathies and Dermatomyositis
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Deutsche Forschungsgemeinschaft
- Bundesministerium für Bildung und Forschung
- Heinrich-Heine-Universität Düsseldorf