抗体偶联药物连接技术的研究进展

Research progress of linkage technology of antibody-drug conjugates

随着抗体修饰技术和选择性偶联技术的发展,抗体偶联药物(ADC)已成为癌症靶向治疗的重要药物之一。连接子连接细胞毒性药物和抗体,是ADC的关键部件之一。连接子与细胞毒性药物主要通过腙键、二硫键、多肽和硫醚连接。通过引入反应性的半胱氨酸、改造二硫键、引入非天然氨基酸、修饰抗体C/N端、修饰氨基酸和糖基对抗体进行改造,实现连接子与抗体的选择性连接。连接技术的发展已成为ADC更新换代和蓬勃发展的关键因素。

With the development of antibody modification technology and selective conjugation technology,antibodydrug conjugates(ADC)have become one kind of the important drugs for cancer targeted therapy.The linker connecting cytotoxic drugs and antibodies is one of the key components of ADC.The conjugation methods of linker to cytotoxic drugs mainly including hydrazone bone,disulfide bone,polypeptide connection and thioether connection.The antibody was modified by introducing reactive cysteine,modifying disulfide bonds,introducing unnatural amino acids,modifying the C/N end of the antibody,and modifying amino acids and glycosylation to realize the selective connection between the linker and the antibody.The development of connection technology has become the key factor for the update and development of ADCs.