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

Abstract

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) F₁ and MRL ^fas/fas mouse models of lupus. CAR T cells were active for 1 year in vivo and were enriched in the CD44⁺CD62L⁺ T cell subset. Adoptively transferred splenic T cells from CAR T cell-treated mice depleted CD19⁺ B cells and reduced disease in naive autoimmune mice, indicating that disease control was cell-mediated. Sustained B cell depletion with CD19-targeted CAR T cell immunotherapy is a stable and effective strategy to treat murine lupus, and its effectiveness should be explored in clinical trials for lupus.