• Georg Schett, Andreas Mackensen, and Dimitrios Mougiakakos.
• 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.
• Lancet. 2023 Nov 25; 402 (10416): 203420442034-2044.

AbstractDespite 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.Copyright © 2023 Elsevier Ltd. All rights reserved.

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