Following a single infusion of CD19-targeting CAR T cells, five patients with SLE showed reduction in disease activity and disease markers; long-term follow-up of these patients and larger trials are now key priorities.

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease whose immunological hallmark is the production of antinuclear antibodies. These bind DNA, RNA and associated proteins, leading to deposition of immune complexes and induction of inflammation, cytokine release and organ damage — with lupus nephritis being among the most serious manifestations. Given that B cells are the source of pathogenic antinuclear antibodies and their generation precedes the clinical onset of SLE, therapeutic strategies have focused on B cell blockade1. Monoclonal antibodies that deplete B cells (anti-CD20) or interfere with their activation and proliferation (by targeting the B lymphocyte stimulator) are effective in some patients2,3, but others will progress to renal failure and, occasionally, death. Treatment failures have been attributed to insufficient depletion of autoreactive B cells, inaccessibility of affected tissues to therapeutic antibodies, and lack of expression of CD20 on the long-lived plasma cells and plasmablasts that produce anti-nuclear antibodies. Deep and durable depletion of autoantibody-producing B cells that enables drug-free remission has therefore been an elusive goal in SLE research.