Therapeutic efficacy of anti-CD19 CAR-T cells in a mouse model of systemic lupus erythematosus
作者机构：Zhejiang University-University of Edinburgh InstituteZhejiang University School of MedicineHaining314400PR China Institute of ImmunologyZhejiang University School of MedicineHangzhou310058PR China Department of RheumatologySir Run Run Shaw HospitalZhejiang University School of MedicineHangzhou310016PR China Innovative Cellular Therapeutics Co.Ltd.Shanghai201203PR China Dr.Li Dak Sum and Yip Yio Chin Center for Stem Cells and Regenerative MedicineZhejiang University School of MedicineHangzhou310058PR China
出 版 物：《Cellular & Molecular Immunology》 (中国免疫学杂志（英文版）)
年 卷 期：2021年第18卷第8期
页 面：1896-1903页
核心收录：
学科分类：0710[理学-生物学] 1004[医学-公共卫生与预防医学(可授医学、理学学位)] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学]
基 金：This work was supported by grants from the National Natural Science Foundation of China(31770954,31530019 to L.L.and 31900628 to Q.X.) the Fundamental Research Funds for the Central Universities(2018XZZX001-12 to L.L.)
主 题：Systemic lupus erythematosus Autoimmune disease Treatment T cells B cells
摘 要：Dysregulated B-cell activation plays pivotal roles in systemic lupus erythematosus(SLE),which makes B-cell depletion a potential strategy for SLE *** clinical success of anti-CD19 CAR-T cells in treating B-cell malignancies has attracted the attention of *** this study,we aimed to investigate the feasibility of applying anti-CD19 CAR-T cell therapy to SLE treatment in a mouse disease *** 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 ***,anti-CD19 CAR-T cells were transferred to MRL-lpr mice before the onset of disease to determine their role in SLE *** 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 *** 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 *** 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 *** 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.
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