决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:B-cell maturation antigen targeting strategies in multiple myeloma treatment, advantages and disadvantages.
就较低的潜在全身和局部副作用而言,BCMA 可被视为免疫治疗方法中理想的靶向分子。
B细胞成熟抗原(BCMA)是肿瘤坏死因子受体超家族17(TNFRSF17)的跨膜糖蛋白,在多发性骨髓瘤(MM)患者及正常人群的浆细胞上均高表达,也是MM的生物标志物。肿瘤坏死因子超家族中的两种蛋白——B细胞活化因子(BAFF)和增殖诱导配体(APRIL)——与BCMA密切相关,在浆细胞存活和MM进展中发挥重要作用。尽管单克隆抗体技术具有较高特异性,但并非所有恶性肿瘤都能使用肿瘤特异性抗原作为靶点。MM表达多种相对特异性抗原,如GPRC5D、MUC1和SLAMF7等;但与正常细胞相比,MM细胞上BCMA表达更高,因此可视为相对特异的标志物。目前用于抗MM治疗的单克隆抗体包括daratumumab、SAR650984和GSK2857916,CAR-T细胞疗法也属于相关治疗工具,本文对其进行综述。此外,本文还评估BCMA及其相关分子的结构、功能和信号转导,以及它们在正常浆细胞和MM发生发展中的作用,并讨论不同代CAR-T靶向这些分子可能导致的副作用。总之,鉴于全身和局部副作用的潜在风险较低,BCMA可视为免疫治疗的理想靶点。
B cell maturation antigen (BCMA), a transmembrane glycoprotein member of the tumor necrosis factor receptor superfamily 17 (TNFRSF17), highly expressed on the plasma cells of Multiple myeloma (MM) patients, as well as the normal population. BCMA is used as a biomarker for MM. Two members of the TNF superfamily proteins, including B-cell activating factor (BAFF) and A proliferation-inducing ligand (APRIL), are closely related to BCMA and play an important role in plasma cell survival and progression of MM. Despite the maximum specificity of the monoclonal antibody technologies, introducing the tumor-specific antigen(s) is not applicable for all malignancies, such as MM that there plenty of relatively specific antigens such as GPCR5D, MUC1, SLAMF7 and etc., but higher expression of BCMA on these cells in comparison with normal ones can be regarded as a relatively exclusive marker. Currently, different monoclonal antibody (mAb) technologies applied in anti-MM therapies such as daratuzumab, SAR650984, GSK2857916, and CAR-T cell therapies are some of these tools that are reviewed in the present manuscript. By the way, the structure, function, and signaling of the BCMA and related molecule(s) role in normal plasma cells and MM development, evaluated as well as the potential side effects of its targeting by different CAR-T cells generations. In conclusion, BCMA can be regarded as an ideal molecule to be targeted in immunotherapeutic methods, regarding lower potential systemic and local side effects.
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