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

M. Doglio (), A. Ugolini, C. Bercher-Brayer, B. Camisa, C. Toma, R. Norata, S. Del Rosso, R. Greco, F. Ciceri, F. Sanvito, M. Casucci, A. A. Manfredi and C. Bonini ()
Additional contact information
M. Doglio: IRCCS San Raffaele Scientific Institute
A. Ugolini: IRCCS San Raffaele Scientific Institute
C. Bercher-Brayer: IRCCS San Raffaele Scientific Institute
B. Camisa: IRCCS San Raffaele Scientific Institute
C. Toma: IRCCS San Raffaele Scientific Institute
R. Norata: IRCCS San Raffaele Scientific Institute
S. Del Rosso: IRCCS San Raffaele Hospital
R. Greco: IRCCS San Raffaele Hospital
F. Ciceri: IRCCS San Raffaele Hospital
F. Sanvito: IRCCS San Raffaele Scientific Institute
M. Casucci: IRCCS San Raffaele Scientific Institute
A. A. Manfredi: IRCCS San Raffaele Scientific Institute
C. Bonini: IRCCS San Raffaele Scientific Institute

Nature Communications, 2024, vol. 15, issue 1, 1-21

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-46448-9

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