Doglio, M., Alexander, T., Del Papa, N. et al. (2 more authors) (2022) New insights in systemic lupus erythematosus: from regulatory T cells to CAR-T-cell strategies. Journal of Allergy and Clinical Immunology, 150 (6). pp. 1289-1301. ISSN 0091-6749
Abstract
Systemic lupus erythematous is a heterogeneous autoimmune disease with potentially multiorgan damage. Its complex etiopathogenesis involves genetic, environmental, and hormonal factors, leading to a loss of self-tolerance with autoantibody production and immune complex formation. Given the relevance of autoreactive B lymphocytes, several therapeutic approaches have been made targeting these cells. However, the disease remains incurable, reflecting an unmet need for effective strategies. Novel therapeutic concepts have been investigated to provide more specific and sustainable disease modification compared with continued immunosuppression. Autologous hematopoietic stem cell transplantation has already provided the proof-of-concept that immunodepletion can lead to durable treatment-free remissions, albeit with significant treatment-related toxicity. In the future, chimeric antigen receptor-T-cell therapies, for example, CD19 chimeric antigen receptor-T, may provide a more effective lymphodepletion and with less toxicity than autologous hematopoietic stem cell transplantation. An emerging field is to enhance immune tolerance by exploiting the suppressive capacities of regulatory T cells, which are dysfunctional in patients with systemic lupus erythematous, and thus resemble promising candidates for adoptive cell therapy. Different approaches have been developed in this area, from polyclonal to genetically engineered regulatory T cells. In this article, we discuss the current evidence and future directions of cellular therapies for the treatment of systemic lupus erythematous, including hematopoietic stem cell transplantation and advanced regulatory T-cell–based cellular therapies.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | © 2022 The Authors. Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives licence (https://creativecommons.org/licenses/by-nc-nd/4.0/). |
Keywords: | Autoimmune diseases; CAR-T-cell therapy; HSCT; autoimmunity; cell therapy; Humans; T-Lymphocytes, Regulatory; Receptors, Chimeric Antigen; Lupus Erythematosus, Systemic |
Dates: |
|
Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > The Medical School (Sheffield) > Division of Genomic Medicine (Sheffield) > Department of Oncology and Metabolism (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 06 Mar 2023 16:02 |
Last Modified: | 06 Mar 2023 16:02 |
Published Version: | http://dx.doi.org/10.1016/j.jaci.2022.08.003 |
Status: | Published |
Publisher: | Elsevier BV |
Refereed: | Yes |
Identification Number: | 10.1016/j.jaci.2022.08.003 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:197020 |