On-line First

J Rheum Dis

Published online January 20, 2025

© Korean College of Rheumatology

Chimeric Antigen Receptor T-cell therapy in systemic autoimmune rheumatic diseases: current insights and future prospects

Bong-Woo Lee, M.D.1* , Eui-Jong Kwon, M.D.2* , Ji Hyeon Ju, M.D., Ph.D.1

Division of Rheumatology, Department of Internal Medicine, 1Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, 2Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Bucheon, Korea

Correspondence to : Ji Hyeon Ju, https://orcid.org/0000-0002-1381-5466
Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Korea. E-mail: juji@catholic.ac.kr

*These authors contributed equally to this work.

Received: October 23, 2024; Revised: November 30, 2024; Accepted: January 3, 2025

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Chimeric Antigen Receptor (CAR) T-cell therapy, revolutionary in treating hematological malignancies, is emerging as a promising approach for systemic autoimmune rheumatic diseases (SARDs). This review examines the potential of CAR T-cell therapy in treating conditions such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and idiopathic inflammatory myopathies (IIMs). The evolution of CAR T cells technology, from first to fifth generation, has enhanced its efficacy and persistence. Early clinical studies in SARDs have shown encouraging results, with some patients achieving drug-free remission. CD19-targeted CAR T cells have demonstrated significant B-cell depletion and clinical improvement in patients with SLE, SSc, and IIMs. Despite promising outcomes, challenges remain, including cytokine release syndrome and the need for careful patient selection. Future directions include exploring dual-targeting CARs, chimeric autoantibody receptors (CAARs), and alternative cell sources like γδ T cells, regulatory T cells, natural killer cells. The integration of CAR-based cell therapy into treatment paradigms of patients with SARDs requires further research to optimize efficacy, mitigate side effects, and identify suitable target biomarkers. While hurdles exist CAR-based cell therapy holds the potential to revolutionize management of patients with SARDs, offering hope for longterm, drug-free remission in these complex autoimmune conditions.

Keywords Chimeric Antigen Receptor T-cell therapy, Autoimmune diseases, Systemic lupus erythematosus, Systemic sclerosis, Idiopathic inflammatory myopathy

Article

On-line First

J Rheum Dis

Published online January 20, 2025

Copyright © Korean College of Rheumatology.

Chimeric Antigen Receptor T-cell therapy in systemic autoimmune rheumatic diseases: current insights and future prospects

Bong-Woo Lee, M.D.1* , Eui-Jong Kwon, M.D.2* , Ji Hyeon Ju, M.D., Ph.D.1

Division of Rheumatology, Department of Internal Medicine, 1Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, 2Bucheon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Bucheon, Korea

Correspondence to:Ji Hyeon Ju, https://orcid.org/0000-0002-1381-5466
Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Korea. E-mail: juji@catholic.ac.kr

*These authors contributed equally to this work.

Received: October 23, 2024; Revised: November 30, 2024; Accepted: January 3, 2025

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Chimeric Antigen Receptor (CAR) T-cell therapy, revolutionary in treating hematological malignancies, is emerging as a promising approach for systemic autoimmune rheumatic diseases (SARDs). This review examines the potential of CAR T-cell therapy in treating conditions such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and idiopathic inflammatory myopathies (IIMs). The evolution of CAR T cells technology, from first to fifth generation, has enhanced its efficacy and persistence. Early clinical studies in SARDs have shown encouraging results, with some patients achieving drug-free remission. CD19-targeted CAR T cells have demonstrated significant B-cell depletion and clinical improvement in patients with SLE, SSc, and IIMs. Despite promising outcomes, challenges remain, including cytokine release syndrome and the need for careful patient selection. Future directions include exploring dual-targeting CARs, chimeric autoantibody receptors (CAARs), and alternative cell sources like γδ T cells, regulatory T cells, natural killer cells. The integration of CAR-based cell therapy into treatment paradigms of patients with SARDs requires further research to optimize efficacy, mitigate side effects, and identify suitable target biomarkers. While hurdles exist CAR-based cell therapy holds the potential to revolutionize management of patients with SARDs, offering hope for longterm, drug-free remission in these complex autoimmune conditions.

Keywords: Chimeric Antigen Receptor T-cell therapy, Autoimmune diseases, Systemic lupus erythematosus, Systemic sclerosis, Idiopathic inflammatory myopathy

JRD
Jan 01, 2025 Vol.32 No.1, pp. 1~7
COVER PICTURE
Cumulative growth of rheumatology members and specialists (1980~2024). Cumulative distribution of the number of the (A) Korean College of Rheumatology members and (B) rheumatology specialists. (J Rheum Dis 2025;32:63-65)

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