CAR-T cells targeting fibroblast activation protein eliminate pathological fibroblasts and preserve cardiac function in a Duchenne Muscular Dystrophy murine model.
Céline Marigny, Gaëlle Revet, Anne Berger, Morgane Boulch, Nathalie Mougenot, Zhenlin Li, Béatrice Corre, Mégane Lemaitre, Axelle Bois, Clara Castelli, Victor Collombat, Ara Parlakian, Marie-Cécile Perier, Adrian Bot, Jonathan A Epstein, Peggy Lafuste, Albert Hagege, Haig Aghajanian, Clément Cochain, Philippe Bousso, Onnik Agbulut, Philippe Menasché
Abstract
Chimeric Antigen Receptor (CAR)-T cells therapy has revolutionized the treatment of hematological cancers and are currently redirected towards non-malignant diseases. If correction of the gene defect remains the cornerstone of the treatment of Duchenne Muscular Dystrophy (DMD), the disease-associated fibrosis can limit its efficacy. We thus assessed the effects of eliminating cardiac fibrosis of DMD by CAR-T cells targeting Fibroblast Activation Protein (FAP), a protein strongly expressed by activated fibroblasts.