抗体偶联药物内吞作用机制的研究进展  

Progress on internalization study of antibody-drug conjugates

作　　者：唐煜[1,2] 王相阳[2] 马晓慧[2] 周芳[1] 王广基[1] 

机构地区：[1]中国药科大学江苏省药物代谢动力学重点实验室,南京210009 [2]天士力集团研究院药理毒理研究中心,天津300402

出　　处：《中国新药杂志》2017年第10期1130-1136,共7页Chinese Journal of New Drugs

摘　　要：抗体偶联药物(antibody-drug conjugate,ADC)由单克隆抗体和小分子细胞毒药物通过化学连接子连接,兼顾了单克隆抗体的选择性和小分子药物的细胞毒效力。ADC进入体内后,可通过单克隆抗体的靶向作用结合于肿瘤表面的靶抗原,经内吞作用进入细胞内,在溶酶体的化学或酶促作用下释放小分子细胞毒药物导致靶细胞死亡。ADC的内吞作用是ADC发挥药效的关键,并且已经成为ADC开发阶段的重要部分。由于缺乏对于ADC内吞作用的整体认识,目前对于内吞效率和内吞机制的研究方法开发存在着诸多挑战。本文对ADC的内吞机制、影响因素和研究方法等方面的进展进行了综合归纳和阐述。Antibody-drug conjugates （ADC） are complex molecules with cytotoxic small molecular drugs covalently bound to monoclonal antibodies via a linker and combining the antigen-targeting specificity of monoclonal antibodies with the cytotoxic potency of chemotherapeutic drugs. ADC molecules bind to the target antigens expressed on the tumor cell surfaces guided by the monoclonal antibody component. The binding ADC molecules can be internalized and subsequently the toxin moieties can be released within the tumor cells via chemical and/or enzymatic reactions to kill the target cells. Internalization of an ADC is critical to its efficacy and now is an important part of its development stage. But due to the lack of overall understanding of ADC internalization, there are so many challenges in the development of research method about internalization and its mechanism. This review will discuss mechanism, influence factors and common methods and developments of ADC internalization.

关 键 词：抗体偶联药物 内吞作用 网格蛋白 流式细胞术 共聚焦显微镜 

分 类 号：R972.6[医药卫生—药品]