CAR T-cell therapy in autoimmune diseases.


Journal

Lancet (London, England)
ISSN: 1474-547X
Titre abrégé: Lancet
Pays: England
ID NLM: 2985213R

Informations de publication

Date de publication:
25 11 2023
Historique:
received: 14 12 2022
revised: 12 04 2023
accepted: 25 05 2023
medline: 27 11 2023
pubmed: 26 9 2023
entrez: 25 9 2023
Statut: ppublish

Résumé

Despite the tremendous progress in the clinical management of autoimmune diseases, many patients do not respond to the currently used treatments. Autoreactive B cells play a key role in the pathogenesis of autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis. B-cell-depleting monoclonal antibodies, such as rituximab, have poor therapeutic efficacy in autoimmune diseases, mainly due to the persistence of autoreactive B cells in lymphatic organs and inflamed tissues. The adoptive transfer of T cells engineered to target tumour cells via chimeric antigen receptors (CARs) has emerged as an effective treatment modality in B-cell malignancies. In the last 2 years treatment with autologous CAR T cells directed against the CD19 antigen has been introduced in therapy of autoimmune disease. CD19 CAR T cells induced a rapid and sustained depletion of circulating B cells, as well as in a complete clinical and serological remission of refractory systemic lupus erythematosus and dermatomyositis. In this paper, we discuss the evolving strategies for targeting autoreactive B cells via CAR T cells, which might be used for targeted therapy in autoimmune diseases.

Identifiants

pubmed: 37748491
pii: S0140-6736(23)01126-1
doi: 10.1016/S0140-6736(23)01126-1
pii:
doi:

Substances chimiques

Rituximab 4F4X42SYQ6
Receptors, Chimeric Antigen 0
Antigens, CD19 0
Receptors, Antigen, T-Cell 0

Types de publication

Journal Article Review Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2034-2044

Informations de copyright

Copyright © 2023 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests GS has received speaker honoraria and consulting fees from Bristol Myers Squibb, Cabaletta, Janssen, Kyverna, Miltenyi, and Novartis. AM has received speaker honoraria and consulting fees from Bristol Myers Squibb, Miltenyi Biomedicine, BioNTech, Kite Pharma, Gilead Sciences, and Novartis. DM has received speaker honoraria and consulting fees from AbbVie, Bristol Myers Squibb, Beigene, Celgene, Gilead, Janssen, Miltenyi, and Novartis. GS is supported by the Deutsche Forschungsgemeinschaft through the Leibniz Award, the research group grants PANDORA FOR2886, and the CRC1483 (EmpkinS), and CRC1181; has obtained funding from the Bundesministerium für Bildung und Forschung through the Mascara project and the EU (ERC Synergy grant 4D Nanoscope); and the IMI funded project RTCure. DM is supported by the Deutsche Forschungsgemeinschaft through the research group grants PANDORA FOR2886, CRC/TRR305 (A03), CRC/TRR221 (A06), RTG2408 (P13), and the grant 404074532.

Auteurs

Georg Schett (G)

Department of Internal Medicine 3-Rheumatology and Immunology, Friedrich Alexander Universität Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany; Deutsches Zentrum Immuntherapie, Friedrich Alexander Universität Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany. Electronic address: georg.schett@uk-erlangen.de.

Andreas Mackensen (A)

Deutsches Zentrum Immuntherapie, Friedrich Alexander Universität Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany; Department of Internal Medicine 5-Hematology and Clinical Oncology, Friedrich Alexander Universität Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany.

Dimitrios Mougiakakos (D)

Department of Hematology and Oncology, Otto-von-Guericke University, Magdeburg, Germany; Health Campus Immunology, Infectiology and Inflammation (GCI(3)), Medical Center, Otto-von-Guericke University, Magdeburg, Germany.

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Classifications MeSH