Reengineering chimeric antigen receptor T cells for targeted therapy of autoimmune disease

Ideally, therapy for autoimmune diseases should eliminate pathogenic autoimmune cells while sparing protective immunity, but feasible strategies for such an approach have been elusive. Here, we show that in the antibody-mediated autoimmune disease pemphigus vulgaris (PV), autoantigen-based chimeric immunoreceptors can direct T cells to kill autoreactive B lymphocytes through the specificity of the B cell receptor (BCR). We engineered human T cells to express a chimeric autoantibody receptor (CAAR), consisting of the PV autoantigen, desmoglein (Dsg) 3, fused to CD137-CD3ζ signaling domains. Dsg3 CAAR-T cells exhibit specific cytotoxicity against cells expressing anti-Dsg3 BCRs in vitro and expand, persist, and…

• DF
  Dermatology Foundation
• DF
  Deutsche Forschungsgemeinschaft
• MD
  Ministero della Salute
• NH
  National Heart, Lung, and Blood Institute

  Award: K12-HL087064
• NI
  National Institute of Arthritis and Musculoskeletal and Skin Diseases

  Awards: F31-AR066456, R01-AR057001, R01-AR055309, T32-AR007465, R01-AR068288