靶向抗肿瘤抗体-药物偶联物研究进展

Development of antibody-drug conjugates as targeted cancer therapeutics

靶向治疗已成为当今肿瘤研究领域的热点。抗体-药物偶联物(antibody drug conjugates,ADC)兼具抗体的高特异性和细胞毒药物对肿瘤的高毒性,代表了新一代抗体技术的发展方向。ADC由"弹头"药物(细胞毒药物)、抗体以及偶联抗体和药物的偶联链3部分组成。ADC利用抗体作为载体将"弹头"药物送至靶部位,并通过细胞内吞效应进入溶酶体,释放出细胞毒性药物,从而达到专一性杀死癌细胞而不损伤正常组织细胞的作用。本文综述近年来ADC研制和发展趋势,并探讨ADC研发过程中的几个可能的关键影响因素。

Targeted therapy is a promising treatment for cancer patients. Antitumor antibody drug conjugates（ADC）, the new generation of antibody technology, combine the target-specificity of monoclonal antibody （mAb） and the highly active cell-killing of drugs, taking advantages of the best characteristics of both components. ADC contain three main components： antibody, linker and cytotoxics （also frequently referred as payload）. Antibodies can recognize and specifically bind to the tumor-specific antigens, leading to an antibody-assisted internalization, and payload release under low pH or the action of lysosomal proteases, so as to achieve the specificity killing of cancer cells without damaging normal tissue cells. This paper reviews the emergence and development of ADC, and discusses several possible key influential factors in the development process of ADC.