2. Academic Validation
  3. Therapeutic efficacy of anti-CD19 CAR-T cells in a mouse model of systemic lupus erythematosus

Therapeutic efficacy of anti-CD19 CAR-T cells in a mouse model of systemic lupus erythematosus

  • Cell Mol Immunol. 2021 Aug;18(8):1896-1903. doi: 10.1038/s41423-020-0472-1.
Xuexiao Jin 1 2 3,  Qin Xu 3,  Chengfei Pu 4,  Kaixiang Zhu 1 2,  Cheng Lu 4,  Yu Jiang 2,  Lei Xiao 4,  Yongmei Han 5,  Linrong Lu 6 7 8 9
Affiliations

Affiliations

  • 1 Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, Haining, 314400, PR China.
  • 2 Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, 310058, PR China.
  • 3 Department of Rheumatology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, PR China.
  • 4 Innovative Cellular Therapeutics Co., Ltd., Shanghai, 201203, PR China.
  • 5 Department of Rheumatology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, PR China. 3408235@zju.edu.cn.
  • 6 Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, Haining, 314400, PR China. lu_linrong@zju.edu.cn.
  • 7 Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, 310058, PR China. lu_linrong@zju.edu.cn.
  • 8 Department of Rheumatology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, PR China. lu_linrong@zju.edu.cn.
  • 9 Dr. Li Dak Sum and Yip Yio Chin Center for Stem Cells and Regenerative Medicine, Zhejiang University School of Medicine, Hangzhou, 310058, PR China. lu_linrong@zju.edu.cn.
PMID: 32472023 DOI: 10.1038/s41423-020-0472-1
Abstract

Dysregulated B-cell activation plays pivotal roles in systemic lupus erythematosus (SLE), which makes B-cell depletion a potential strategy for SLE treatment. The clinical success of anti-CD19 CAR-T cells in treating B-cell malignancies has attracted the attention of researchers. In this study, we aimed to investigate the feasibility of applying anti-CD19 CAR-T cell therapy to SLE treatment in a mouse disease model. We constructed murine anti-CD19 CARs with either CD28 or 4-1BB as the intracellular costimulatory motif and evaluated the therapeutic function of the corresponding CAR-T cells by infusing them into MRL-lpr mice. Furthermore, anti-CD19 CAR-T cells were transferred to MRL-lpr mice before the onset of disease to determine their role in SLE prevention. According to our observations, compared with antibody treatment, the adoptive transfer of our anti-CD19 CAR-T cells showed a more sustained B-cell-depletion effect in MRL-lpr mice. The transfer of syngeneic anti-CD19 CAR-T cells not only prevented disease pathogenesis before the onset of disease symptoms but also displayed therapeutic benefits at a later stage after disease progression. We also tried to optimize the treatment strategy and found that compared with CAR-T cells with the CD28 costimulatory motif, CAR-T cells with the 4-1BB costimulatory motif showed better therapeutic efficiency without cell enrichment. Taken together, these results show that anti-CD19 CAR-T cell therapy was effective in the prevention and treatment of a murine model of SLE, indicating its potential for clinical use in patients.

Keywords

Autoimmune disease; B cells; Systemic lupus erythematosus; T cells; Treatment.

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