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Review
. 2025 May 10;27(1):102.
doi: 10.1186/s13075-025-03564-1.

CAR-T cell therapy for juvenile-onset autoimmune diseases: a promising future?

Maurine Jouret  1 , Sebastien Viel  2   3 , Benjamin Fournier  4 , Sarah Benezech  2   5 , Jérome Avouac  6   7 , Marc Scherlinger  8   9 , Alexandre Belot  10   11 ; C3I consortium
Collaborators, Affiliations
Review

CAR-T cell therapy for juvenile-onset autoimmune diseases: a promising future?

Maurine Jouret et al. Arthritis Res Ther. .

Abstract

Chimeric antigen receptor (CAR) T-cell therapy targeting B cells has shown promising results, including drug-free remission, in adult-onset autoimmune diseases. Extending this therapeutic approach to the pediatric population, particularly for juvenile autoimmune diseases, presents an exciting opportunity. However, challenges specific to juvenile-onset autoimmune conditions, such as long-term adverse events, heightened disease activity, and the imperative to reduce steroid exposure, must be considered. While this strategy appears viable for these severe conditions, the limited data available for this population and the absence of evidence on cases with a high genetic component, such as monogenic lupus, represent significant challenges. Most monogenic lupus cases are associated with innate immune defects, and the involvement of B cells in these genetic anomalies remains poorly understood. In this review, we examine the potential indications, current knowledge, and limitations of CAR-T cell therapy in juvenile-onset autoimmune diseases, extending the discussion beyond early-onset lupus.

Keywords: Autoimmunity; B cells; CAR-T cells; CD19; Children; Juvenile dermatomyositis; Lupus; Monogenic lupus.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: MJ is a consultant for Novartis. MS is a consultant for Abbvie, Amgen, AstraZeneca, Biogen, Bristol Myers Squibb, Fresenius Kabi, Galapagos, Innate Pharma, Nordic Pharma, Novartis, Sandoz. JA: Honoraria: Galapagos, Lilly, Pfizer, Abbvie, Bristol-Myers Squibb, Sanofi, Roche-Chugai, Nordic Pharma, Medac, Novartis, Biogen, Fresenius Kabi, Janssen, and MSD. Research grants: Bristol-Myers Squibb, Pfizer (Passerelle), Novartis (Dreamer), Fresenius Kabi, Galapagos, Nordic Pharma. AB is a consultant for Kabi, Roche Chugai, GlaxoSmithKline, AbbVie, Novartis, and Boehringer Ingelheim.

Figures

Fig. 1
Fig. 1
Illustration of the treatment pathway for patients with severe early-onset autoimmune diseases that are refractory to conventional treatments, with CAR-T cell therapy serving as a salvage option. To optimize CAR-T cell expansion, lymphodepletion is induced using fludarabine and cyclophosphamide which carries a risk of disease exacerbation. Following CAR-T cell infusion, patients commonly experience a transient period of bone marrow aplasia, increasing susceptibility to infections. The expansion of CAR-T cells leads to the targeted depletion of autoreactive B lymphocytes. However, this process may also trigger the release of cytokines, potentially leading to cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Lymphocyte reconstitution occurs progressively over the course of several weeks, though the timeline may vary among patients. The reconstituted B cells are naive and no longer produce autoreactive antibodies, leading to both clinical and biological remission, thereby eliminating the need for ongoing immunosuppressive therapy. Figure created with Biorender.com
See this image and copyright information in PMC

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