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

Düsing C, Györfi AH, Stütz AN, Lahu LM, Deicher FS, Li YN, Bruch PM, Matei AE, Micu A, Filla T, Koziel S, Hölscher AS, Röhrich M, Lorenz HM, Cramer M, Antoch G, Timm J, Abusabha Y, Ruck T, Homey B, Kreuter A, Buehring B, Radujkovic A, Heußel CP, Hagen M, Grieshaber Bouyer R, Schett G, Brunn A, Dietrich S, Merkt W, Distler JH (2026)

Publication Type: Journal article

Publication year: 2026

Journal

Nature Medicine Nature Publishing Group

DOI: 10.1038/s41591-026-04238-4

Abstract

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 with CRIS profile

Melanie Hagen Department of Medicine 3 – Rheumatology and Immunology Ricardo Grieshaber Bouyer Professur für Klinische Systemimmunologie Georg Schett Lehrstuhl für Innere Medizin III

Involved external institutions

Universitätsklinikum Düsseldorf DE Germany (DE) Heinrich-Heine-Universität Düsseldorf DE Germany (DE) Universitätsmedizin der Johannes Gutenberg-Universität Mainz DE Germany (DE) Universitätsklinikum Heidelberg DE Germany (DE) Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil DE Germany (DE) Universität Witten/Herdecke DE Germany (DE)

How to cite

APA:

Düsing, C., Györfi, A.H., Stütz, A.N., Lahu, L.M., Deicher, F.S., Li, Y.N.,... Distler, J.H. (2026). Bispecific T cell engagers for treatment-refractory autoimmune connective tissue diseases. Nature Medicine. https://doi.org/10.1038/s41591-026-04238-4

MLA:

Düsing, Christina, et al. "Bispecific T cell engagers for treatment-refractory autoimmune connective tissue diseases." Nature Medicine (2026).

BibTeX: Download