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Chimeric antigen receptor T cell therapy for autoimmune disease

Nature Reviews Immunology (2024)Cite this article

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Abstract

Infusion of T cells engineered to express chimeric antigen receptors (CARs) that target B cells has proven to be a successful treatment for B cell malignancies. This success inspired the development of CAR T cells to selectively deplete or modulate the aberrant immune responses that underlie autoimmune disease. Promising results are emerging from clinical trials of CAR T cells targeting the B cell protein CD19 in patients with B cell-driven autoimmune diseases. Further approaches are being designed to extend the application and improve safety of CAR T cell therapy in the setting of autoimmunity, including the use of chimeric autoantibody receptors to selectively deplete autoantigen-specific B cells and the use of regulatory T cells engineered to express antigen-specific CARs for targeted immune modulation. Here, we highlight important considerations, such as optimal target cell populations, CAR construct design, acceptable toxicities and potential for lasting immune reset, that will inform the eventual safe adoption of CAR T cell therapy for the treatment of autoimmune diseases.

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Fig. 1: Expression of protein markers during B cell development and differentiation.
Fig. 2: Key components of CARs.
Fig. 3: Select types of CAR constructs.
Fig. 4: Engineered Treg cell properties.

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Authors and Affiliations

  1. Kyverna Therapeutics Inc., Emeryville, CA, USA

    James B. Chung & Dominic Borie

  2. Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    Jennifer N. Brudno & James N. Kochenderfer

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  1. James B. Chung
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J.B.C. and D.B. are employees of Kyverna Therapeutics. J.N.B. is a scientific adviser for Kyverna Therapeutics (unpaid position). J.N.K is principal investigator of research agreements between the National Cancer Institute and Kite Pharma (Gilead Sciences) and Celgene (Bristol Myers Squibb); has received royalties from Kite, Celgene and Kyverna Therapeutics; and is also an inventor on multiple patent applications and patents for chimeric antigen receptors (CARs).

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Nature Reviews Immunology thanks Megan Levings, Marko Radic and the other anonymous reviewers for their contribution to the peer review of this work.

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Chung, J.B., Brudno, J.N., Borie, D. et al. Chimeric antigen receptor T cell therapy for autoimmune disease. Nat Rev Immunol (2024). https://doi.org/10.1038/s41577-024-01035-3

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