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Roads and detours for CAR T cell therapy in autoimmune diseases

Nature Reviews Drug Discovery (2026)Cite this article

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Abstract

Chimeric antigen receptor (CAR) T cell therapy has been highly effective in eradicating malignant B cells in cancer, and this success has prompted an extension of the approach to areas beyond oncology. In pioneering studies, CAR T cells targeting the B cell marker CD19 demonstrated robust efficacy as treatment for the autoimmune disease systemic lupus erythematosus. Patients who received anti-CD19 CAR T cells experienced remission of most or all clinical manifestations and discontinued prior medications. These results have spurred intense interest in extending these observations to larger patient cohorts and other autoimmune conditions. More nuanced strategies for use of CARs in autoimmunity have also been developed. Here, we offer insight into the role of B cells in the pathophysiology of autoimmunity and present an overview of preclinical studies and clinical trials that use engineered cell therapy for autoimmune disorders. In discussing the prospects and challenges of this emerging field, a view emerges in which the promise of clinical efficacy invites careful consideration of potential pitfalls.

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Fig. 1: Composite nature of CARs.
Fig. 2: Bubble plot of CAR T cell trials in autoimmune diseases, relating targets to indications.
Fig. 3: Alternative CAR T cell approaches.

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Acknowledgements

The authors acknowledge information gathered by J. J. Knox, University of Pennsylvania, that was used in Table 2. A.B. acknowledges funding from the European Research Council (ERC) (08930382000), Boaz and Varda Dotan, and the Israeli Ministry of Health (00370000015). R.S.D. was supported in part by the Leukaemia and Lymphoma Society (LLS). M.S. is supported by the Bettencourt-Schueller Foundation, the INSERM, Ecole de l’INSERM Bettencourt-Schueller, the FOREUM foundation and the Arthritis Pierre Coubertin foundation. S.G. is supported by the American Lebanese Syrian Associated Charities (ALSAC). A.T. is supported by 1K08CA279927-01A1 from the National Institutes of Health (NIH). M.R. receives research support from the Alliance for Lupus Research, LLS and the Oxnard Foundation.

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Authors and Affiliations

  1. Service de Rhumatologie, Hôpital Cochin, APHP, Centre Université Paris Cité, Paris, France

    Jérôme Avouac

  2. The School of Neurobiology, Biochemistry and Biophysics, Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel

    Adi Barzel

  3. Guggenheim Securities, New York, NY, USA

    Delma Caiati & Yatin Suneja

  4. Departments of Medicine, Microbiology, and Biochemistry & Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL, USA

    Randall S. Davis

  5. Department of Bone Marrow Transplantation & Cellular Therapy, St. Jude Children’s Research Hospital, Memphis, TN, USA

    Stephen Gottschalk & Aimee Talleur

  6. Department of Internal Medicine 3 — Rheumatology and Immunology, Universitätsklinikum Erlangen and Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Erlangen, Germany

    Ricardo Grieshaber-Bouyer

  7. Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Xuming Mao & Eline T. Luning Prak

  8. Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN, USA

    Marko Radic

  9. Rheumatology Department, National Reference Center for Rare Autoimmune Systemic Diseases, RESO, Strasbourg University Hospital, Strasbourg, France

    Marc Scherlinger

  10. Department of Medicine, University of Tennessee Health Science Center, Memphis, TN, USA

    Amber L. Thacker

  11. The Jackson Laboratory, Farmington, CT, USA

    Derya Unutmaz

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  1. Jérôme Avouac
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All authors contributed equally to all aspects of the article and are listed alphabetically.

Corresponding author

Correspondence to Marko Radic.

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Competing interests

M.S. is a consultant for Abbvie, Amgen, AstraZeneca, Biogen, BMS, Fresenius, Galapagos, GSK, Innate Pharma, Nordic Pharma, Novartis, Roche and Sandoz. S.G. is a member of the Data Safety Monitoring Board (DSMB) of Immatics, serves on the Scientific Advisory Board of Be Biopharma, served as a consultant for CARGO Therapeutics within the last 12 months, and has patents and patent applications in the fields of T cell and/or gene therapy for cancer. M.R. has consulted for Bain Capital, Guidepoint Global LLC and NVP Associates. The other authors declare no additional competing interests.

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Avouac, J., Barzel, A., Caiati, D. et al. Roads and detours for CAR T cell therapy in autoimmune diseases. Nat Rev Drug Discov (2026). https://doi.org/10.1038/s41573-025-01349-4

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