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- W2997823818 abstract "Objective: To construct the BCMA-CAR using the B-cell maturation antigen (BCMA) specific ligand APRIL as antigen binding region and to validate the effect of BCMA-CAR modified T cells (BCMA-CAR-T) on myeloma cells. Methods: The BCMA-CAR was constructed using the BCMA specific ligand APRIL as antigen binding domain and 4-1BB as the costimulatory domain. The specific cytotoxicity against BCMA(+) myeloma cell lines and primary multiple myeloma (MM) cells in vitro were evaluated. In addition, BCMA(+) myeloma xenograft mouse model was established to assess the anti-tumor effect of BCMA-CAR-T cell therapy in vivo. Results: BCMA-CAR-T cells could specifically kill BCMA(+) myeloma cell lines (For BCMA-CAR-T cells, BCMA(+) cells are almost undetectable in the E∶T ratio of 1∶4) and MM patients' bone marrow mononuclear cells (the proportion of residual cells in BCMA-CAR-T and vector-T groups was 16.0% vs 66.85%, P=0.003) with significant degranulation (CAR-T and vector-T cells cocultured with MM1.S, H929 and U266 had degranulation levels of 33.30% vs 5.62%, 16.97% vs 2.95% and 25.87% vs 2.97%, respectively, P<0.001) and cytokines release (P<0.01) in vitro. In a human BCMA(+) myeloma xenograft mouse model, BCMA-CAR-T cells could significantly prolong the survival of mice (The median survival time of mice treated with BCMA-CAR-T and vector-T cells was 87.5 days and 67.5 days, respectively, P<0.001) . Conclusion: The ligand-based BCMA-CAR-T cells could be a promising strategy for BCMA(+) multiple myeloma treatment.目的： 构建以B细胞成熟抗原（BCMA）的特异性配体APRIL为抗原结合区的BCMA-CAR，并验证该BCMA-CAR修饰的T细胞（BCMA-CAR-T）对多发性骨髓瘤的作用。 方法： 以BCMA的特异性配体APRIL为抗原结合区、4-1BB为共刺激分子而构建BCMA-CAR，体外实验验证BCMA-CAR-T细胞对BCMA(+)骨髓瘤细胞系和原代骨髓瘤细胞的特异性细胞毒作用。此外，构建BCMA(+)骨髓瘤小鼠模型并评价BCMA-CAR-T细胞的体内抗肿瘤效应。 结果： BCMA-CAR-T细胞能特异性杀伤BCMA(+)骨髓瘤细胞系（当效靶比为1∶4时，BCMA-CAR-T细胞组中BCMA(+)细胞几乎检测不到）和骨髓瘤患者的骨髓单个核细胞（BCMA-CAR-T和空载组T细胞的残余细胞比例分别为16.00%和66.85%，P=0.003），并伴随显著的脱颗粒效应（CAR-T和空载组T细胞与MM1.S、H929、U266共培养的脱颗粒水平分别为33.30%对5.62%、16.97%对2.95%、25.87%对2.97%，P值均<0.001）和细胞因子释放（P值均<0.01）。在治疗人BCMA(+)骨髓瘤小鼠移植模型中，BCMA-CAR-T细胞可显著延长小鼠的生存期（BCMA-CAR-T和空载组T细胞治疗小鼠的中位生存期分别为87.5 d、67.5 d，P<0.001）。 结论： 以APRIL为抗原识别区的BCMA-CAR-T细胞有望成为治疗BCMA(+)多发性骨髓瘤的理想策略。." @default.
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- W2997823818 date "2019-10-14" @default.
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- W2997823818 title "[Targeting BCMA in multiple myeloma using chimeric antigen receptor-engineered T cells]." @default.
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- W2997823818 doi "https://doi.org/10.3760/cma.j.issn.0253-2727.2019.10.002" @default.
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