CD19-Targeted CAR T Cells in Refractory Systemic Lupus Erythematosus
Dimitrios Mougiakakos, Gerhard Krönke, Simon Völkl, Sascha Kretschmann, Michael Aigner, Soraya Kharboutli, Sebastian Böltz, Bernhard Manger, Andréas Mackensen, Georg Schett
Abstract
To the Editor: Systemic lupus erythematosus (SLE) is a severe autoimmune disease that predominantly affects young women. SLE is characterized by the formation of autoantibodies and immune complex-mediated inflammation and organ damage. Although autoreactive B cells play a key role in the pathogenesis of SLE, B-cell depletion by antibodies has only limited therapeutic efficacy. 1 This paradox has been attributed to the inaccessibility and persistence of autoreactive B cells within lymphatic organs and inflamed tissues 2 or the pathologic role of CD20-negative plasma cells, which may act as an additional source of autoantibodies in patients with SLE. 3 Chimeric antigen receptor (CAR)-modified T cells that have been genetically engineered to recognize CD19 and other B-cell surface antigens have emerged as a powerful tool for the treatment of relapsed or refractory B-cell cancers. 4 This technological breakthrough, together with recent convincing data on the role of B cells in disease pathogenesis derived from preclinical lupus models, 5 provides a rationale for the use of CAR T-cell therapies in patients with SLE.