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Regulatory T cells expressing CD19-targeted chimeric antigen receptor restore homeostasis in Systemic Lupus Erythematosus

2024; Nature Portfolio; Volume: 15; Issue: 1 Linguagem: Inglês

10.1038/s41467-024-46448-9

2041-1723

Matteo Doglio, Alessio Ugolini, Clara Bercher-Brayer, Barbara Camisa, T. Constantin, Rossana Norata, Stefano Rosso, Raffaella Greco, Fabio Ciceri, Francesca Sanvito, Monica Casucci, Angelo A. Manfredi, Chiara Bonini,

Immune Cell Function and Interaction

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.