Bispecific T cell engager therapy for refractory rheumatoid arthritis

Bucci L, Hagen M, Rothe T, Raimondo MG, Fagni F, Tur C, Wirsching A, Wacker J, Wilhelm A, Auger JP, Pachowsky M, Eckstein M, Alivernini S, Zoli A, Krönke G, Uderhardt S, Bozec A, D’Agostino MA, Schett G, Grieshaber Bouyer R (2024)

Publication Language: English

Publication Type: Journal article

Publication year: 2024

Journal

Nature Medicine Nature Publishing Group

Book Volume: 30

Pages Range: 1593-1601

Journal Issue: 6

DOI: 10.1038/s41591-024-02964-1

Abstract

Bispecific T cell engagers (BiTEs) kill B cells by engaging T cells. BiTEs are highly effective in acute lymphoblastic leukemia. Here we treated six patients with multidrug-resistant rheumatoid arthritis (RA) with the CD19xCD3 BiTE blinatumomab under compassionate use. Low doses of blinatumomab led to B cell depletion and concomitant decrease of T cells, documenting their engager function. Treatment was safe, with brief increase in body temperature and acute phase proteins during first infusion but no signs of clinically relevant cytokine-release syndrome. Blinatumomab led to a rapid decline in RA clinical disease activity in all patients, improved synovitis in ultrasound and FAPI-PET-CT and reduced autoantibodies. High-dimensional flow cytometry analysis of B cells documented an immune reset with depletion of activated memory B cells, which were replaced by nonclass-switched IgD-positive naïve B cells. Together, these data suggest the feasibility and potential for BiTEs to treat RA. This approach warrants further exploration on other B-cell-mediated autoimmune diseases.

Authors with CRIS profile

Laura Bucci Department of Medicine 3 – Rheumatology and Immunology Melanie Hagen Department of Medicine 3 – Rheumatology and Immunology Tobias Rothe Department of Medicine 3 – Rheumatology and Immunology Maria Gabriella Raimondo Department of Medicine 3 – Rheumatology and Immunology Filippo Fagni Department of Medicine 3 – Rheumatology and Immunology Artur Wilhelm Department of Medicine 3 – Rheumatology and Immunology Jean-Philippe Auger Department of Medicine 3 – Rheumatology and Immunology Milena Pachowsky Department of Medicine 3 – Rheumatology and Immunology Markus Eckstein Institute of Pathology Gerhard Krönke Department of Medicine 3 – Rheumatology and Immunology Stefan Uderhardt Department of Medicine 3 – Rheumatology and Immunology Aline Bozec Professur für Experimentelle Immuntherapie Georg Schett Lehrstuhl für Innere Medizin III Ricardo Grieshaber Bouyer

Involved external institutions

Fondazione Policlinico Universitario Agostino Gemelli IRCCS IT Italy (IT)

How to cite

APA:

Bucci, L., Hagen, M., Rothe, T., Raimondo, M.G., Fagni, F., Tur, C.,... Grieshaber Bouyer, R. (2024). Bispecific T cell engager therapy for refractory rheumatoid arthritis. Nature Medicine, 30(6), 1593-1601. https://doi.org/10.1038/s41591-024-02964-1

MLA:

Bucci, Laura, et al. "Bispecific T cell engager therapy for refractory rheumatoid arthritis." Nature Medicine 30.6 (2024): 1593-1601.

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