CD19-Targeted CAR T Cells in Refractory Systemic Lupus Erythematosus

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. 1This 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. 4This 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.We report here on the use of autologous CD19 CAR T cells in the treatment of an autoimmune disease.A 20-year-old woman with severe and refractory SLE presented with active lupus nephritis (World Health Organization class IIIA, indicating focal proliferative disease with active lesions), nephrotic syndrome, pericarditis, pleurisy, rash, arthritis, and a history of Libman-Sacks endocarditis.Previous treatments with hydroxychloroquine, high-dose glucocorticoids, cyclophosphamide, mycophenolate mofetil, and tacrolimus, as well as the B-cell-targeting therapies belimumab and rituximab, did not control symptoms, deplete B cells, or abrogate autoimmunity (Fig. S1 in the