These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: [Targeting BCMA in multiple myeloma using chimeric antigen receptor-engineered T cells].
    Author: Zhong MJ, Xu YX, Xing HY, Tang KJ, Tian Z, Rao Q, Wang M, Wang JX.
    Journal: Zhonghua Xue Ye Xue Za Zhi; 2019 Oct 14; 40(10):804-811. PubMed ID: 31775477.
    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。.
    [Abstract] [Full Text] [Related] [New Search]