1. Regulatory T cells expressing CD19-targeted chimeric antigen receptor restore homeostasis in Systemic Lupus Erythematosus.
- Author
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Doglio, M., Ugolini, A., Bercher-Brayer, C., Camisa, B., Toma, C., Norata, R., Del Rosso, S., Greco, R., Ciceri, F., Sanvito, F., Casucci, M., Manfredi, A. A., and Bonini, C.
- Subjects
SYSTEMIC lupus erythematosus ,B cells ,REGULATORY T cells ,T cells ,CHIMERIC antigen receptors ,T cell receptors ,IMMUNOLOGICAL tolerance ,IMMUNE system ,HOMEOSTASIS - Abstract
Systemic Lupus Erythematosus (SLE) is a progressive disease leading to immune-mediated tissue damage, associated with an alteration of lymphoid organs. Therapeutic strategies involving regulatory T (Treg) lymphocytes, which physiologically quench autoimmunity and support long-term immune tolerance, are considered, as conventional treatment often fails. We describe here a therapeutic strategy based on Tregs overexpressing FoxP3 and harboring anti-CD19 CAR (Fox19CAR-Tregs). Fox19CAR-Tregs efficiently suppress proliferation and activity of B cells in vitro, which are relevant for SLE pathogenesis. In an humanized mouse model of SLE, a single infusion of Fox19CAR-Tregs restricts autoantibody generation, delay lymphopenia (a key feature of SLE) and restore the human immune system composition in lymphoid organs, without detectable toxicity. Although a short survival, SLE target organs appear to be protected. In summary, Fox19CAR-Tregs can break the vicious cycle leading to autoimmunity and persistent tissue damage, representing an efficacious and safe strategy allowing restoration of homeostasis in SLE. Systemic Lupus Erythematosus (SLE) is a chronic and progressive autoimmune disease characterized by abnormally activated B cells causing organ damage. Here authors introduce an adoptive cell therapy involving regulatory T cells overexpressing FoxP3 and harboring an anti-CD19 CAR to inhibit pathological B cells and thus tissue-harming autoimmunity in a humanized mouse model. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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