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, Francesco Giorgianni, James N. Kochenderfer, Tony Marion, Lorraine Albritton, Marko Radic

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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) F 1 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.

Original languageEnglish (US)
Article numbereaav1648
JournalScience Translational Medicine
Volume11
Issue number482
DOIs
StatePublished - Jan 1 2019

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T-Cell Antigen Receptor
B-Lymphocytes
Clinical Trials
Therapeutics
Antigen Receptors
T-Lymphocyte Subsets
Autoantibodies
Immunotherapy
Anti-Idiotypic Antibodies
T-Lymphocytes

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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Sustained B cell depletion by CD19-targeted CAR T cells is a highly effective treatment for murine lupus. / Kansal, Rita; Richardson, Noah; Neeli, Indira; Khawaja, Saleem; Chamberlain, Damian; Ghani, Marium; Ghani, Qurat ul ain; Balazs, Louisa; Beranova, Sarka; Giorgianni, Francesco; Kochenderfer, James N.; Marion, Tony; Albritton, Lorraine; Radic, Marko.

In: Science Translational Medicine, Vol. 11, No. 482, eaav1648, 01.01.2019.

Research output: Contribution to journalArticle

Kansal, Rita ; Richardson, Noah ; Neeli, Indira ; Khawaja, Saleem ; Chamberlain, Damian ; Ghani, Marium ; Ghani, Qurat ul ain ; Balazs, Louisa ; Beranova, Sarka ; Giorgianni, Francesco ; Kochenderfer, James N. ; Marion, Tony ; Albritton, Lorraine ; Radic, Marko. / Sustained B cell depletion by CD19-targeted CAR T cells is a highly effective treatment for murine lupus. In: Science Translational Medicine. 2019 ; Vol. 11, No. 482.
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