Sustained B cell depletion by CD19-targeted CAR T cells is a highly effective treatment for murine lupus
Rita Kansal, Noah Richardson, Indira Neeli, Saleem Khawaja, Damian Chamberlain, Marium Ghani, Qurat-Ul-Ain Ghani, Louisa Balazs, Sarka Beranova-Giorgianni, Francesco Giorgianni, James N Kochenderfer, Tony Marion, Lorraine M Albritton, Marko Radic, Rita Kansal, Noah Richardson, Indira Neeli, Saleem Khawaja, Damian Chamberlain, Marium Ghani, Qurat-Ul-Ain Ghani, Louisa Balazs, Sarka Beranova-Giorgianni, Francesco Giorgianni, James N Kochenderfer, Tony Marion, Lorraine M Albritton, Marko Radic
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.
Conflict of interest statement
Competing interests: UTHSC filed a patent application, no. 65022–274929, titled “Use of Anti-CD19 CAR T Cells in Lupus.” (M.R., inventor). J.N.K. has patent applications for CARs targeting human CD19.
Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
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