Bispecific T cell engager therapy for refractory rheumatoid arthritis.
Nat Med
; 30(6): 1593-1601, 2024 Jun.
Article
en En
| MEDLINE
| ID: mdl-38671240
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Artritis Reumatoide
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Linfocitos B
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Linfocitos T
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Anticuerpos Biespecíficos
Límite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Nat Med
/
Nat. med
/
Nature medicine
Asunto de la revista:
BIOLOGIA MOLECULAR
/
MEDICINA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Alemania