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  • Review Article
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Advancements and challenges in CAR T cell therapy in autoimmune diseases

Nature Reviews Rheumatology volume 20, pages 531–544 (2024)Cite this article

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Abstract

Chimeric antigen receptor (CAR) T cells are highly effective at targeting and eliminating cells of the B cell lineage. CAR T cell therapy has become a standard-of-care treatment for patients with relapsed or refractory B cell malignancies. In addition, the administration of genetically modified T cells with the capacity to deplete B cells and/or plasma cells has tremendous therapeutic potential in autoimmune diseases. In the past few years, CD19-based and B cell maturation antigen (BCMA)-based CAR T cell therapies have been applied to various B cell-mediated autoimmune diseases including systemic lupus erythematosus, idiopathic inflammatory myopathy, systemic sclerosis, neuromyelitis optica spectrum disorder, myasthenia gravis and multiple sclerosis. The scientific rationale behind this approach is that deep depletion of B cells, including autoreactive B cell clones, could restore normal immune function, referred to as an immune reset. In this Review, we discuss important aspects of CAR T cell therapy in autoimmune disease, including considerations relating to patient selection, safety, efficacy and medical management. These considerations are based on the early experiences of CAR T cell therapy in autoimmune diseases, and as the field of CAR T cell therapy in autoimmune diseases continues to rapidly evolve, these issues will remain subject to ongoing refinement and adaptation.

Key points

  • Chimeric antigen receptor (CAR)-expressing cells provide a new and powerful treatment strategy for severe forms of various autoimmune diseases.

  • The CAR-expressing cells applied so far have typically been T cells that recognize B cell-specific or plasma cell-specific antigens such as CD19 or BCMA (B cell maturation antigen), respectively.

  • Currently, most information on the treatment of autoimmune disease with CAR-expressing cells comes from the treatment of patients with autologous CD19-targeting CAR T cells.

  • The success of treating autoimmune disease with CAR-expressing cells is dependent on various pre-procedural, procedural and post-procedural factors; these factors are important considerations that warrant further investigation in future studies.

  • Critical patient selection and careful monitoring for both efficacy and toxicity are paramount for successful treatment with CAR-expressing cells.

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Fig. 1: Vector constructs used for CAR T cell generation in autoimmune disease.
Fig. 2: Spectrum of CAR-based treatment approaches.
Fig. 3: Methods of therapeutic B cell depletion and functional consequences.

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Author information

Authors and Affiliations

  1. Department of Internal Medicine 3 - Rheumatology and Immunology, FAU Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany

    Georg Schett & Jule Taubmann

  2. Deutsches Zentrum Immuntherapie, Universitätsklinikum Erlangen, Friedrich-Alexander University (FAU) Erlangen-Nürnberg, Erlangen, Germany

    Georg Schett, Fabian Müller, Jule Taubmann & Andreas Mackensen

  3. Department of Internal Medicine 5 – Hematology and Oncology, FAU Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany

    Fabian Müller & Andreas Mackensen

  4. Department of Neurology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China

    Wei Wang

  5. Department of Rheumatology, Northwell Health, Great Neck, New York, NJ, USA

    Rich A. Furie

  6. Department of Neurology, St. Josef-Hospital Bochum, Ruhr-University Bochum, Bochum, Germany

    Ralf Gold

  7. Department of Neurology, Otto-von-Guericke University Magdeburg, Magdeburg, Germany

    Aiden Haghikia

  8. Division of Rheumatology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Peter A. Merkel

  9. Division of Epidemiology, Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, PA, USA

    Peter A. Merkel

  10. Division of Rheumatology, UMass Memorial Health, Worcester, MA, USA

    Roberto Caricchio

  11. Department of Rheumatology, Catholic University of Sacred Heart, Rome, Italy

    Maria-Antonietta D’Agostino

  12. Department of Paediatric Hematology and Oncology, Bambino Gesù Children’s Hospital, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) and Catholic University of the Sacred Heart, Rome, Italy

    Franco Locatelli

  13. Center for Cellular Immunology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Carl H. June

  14. Department of Hematology, Oncology, and Cell Therapy, Otto-von-Guericke University Magdeburg, Magdeburg, Germany

    Dimitrios Mougiakakos

  15. Health Campus Immunology, Infectiology and Inflammation, Medical Center, Otto-von-Guericke University, Magdeburg, Germany

    Dimitrios Mougiakakos

Authors
  1. Georg Schett
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  2. Fabian Müller
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  3. Jule Taubmann
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  4. Andreas Mackensen
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  5. Wei Wang
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  6. Rich A. Furie
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  7. Ralf Gold
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  8. Aiden Haghikia
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  9. Peter A. Merkel
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  10. Roberto Caricchio
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  11. Maria-Antonietta D’Agostino
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  12. Franco Locatelli
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  13. Carl H. June
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  14. Dimitrios Mougiakakos
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Contributions

All authors wrote the article. G.S. researched data for the article, contributed substantially to discussion of the content and reviewed and/or edited the manuscript before submission.

Corresponding author

Correspondence to Georg Schett.

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Nature Reviews Rheumatology thanks Raffaella Greco, who co-reviewed with Giorgio Orofino; Marko Radic; E. Hachulla; and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Schett, G., Müller, F., Taubmann, J. et al. Advancements and challenges in CAR T cell therapy in autoimmune diseases. Nat Rev Rheumatol 20, 531–544 (2024). https://doi.org/10.1038/s41584-024-01139-z

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