Sustained B cell depletion by CD19-targeted CAR T cells is a highly effective treatment for murine lupus.

The failure of anti-CD20 antibody (Rituximab) as therapy for lupus may be attributed to the transient and incomplete B cell depletion achieved in clinical trials. Here, using an alternative approach, we report that complete and sustained CD19 B cell depletion is a highly effective therapy in lupus models. CD8 T cells expressing CD19-targeted chimeric antigen receptors (CARs) persistently depleted CD19 B cells, eliminated autoantibody production, reversed disease manifestations in target organs, and extended life spans well beyond normal in the (NZB × NZW) F and MRL mouse models of lupus.