抗体偶联药物（antibody-drug conjugates, ADC）以其特异性和高效性受到国内外制药业的青睐，但其由抗体、毒素和连接物组成的复杂结构，为ADC研究带来了成药性难于预测的困难，仅有的三个上市品种已有一个撤市。抗体的性质、毒素的代谢特点和连接物属性等，都能影响ADC的药代动力学与药效学性质，进而影响成药性。然而，由于上述诸多因素与ADC成药性之间的规律研究十分不足，亟需研究者从ADC活性机制出发，挖掘直接关联ADC活性的深层次关键因素（如内吞率、药物释放率等）。本课题组已有研究表明ADC的细胞水平代谢能够表征其最终活性，相关研究成果已发表在ADVANCED MATERIALS（IF 14.8），本项目拟在此基础上进一步研究ADC细胞代谢动力学对其药效学的作用机理，把握其在细胞水平和动物水平发挥活性的关键因素，为最终总结ADC成药性早期评价规律奠定坚实基础。

Antibody-drug conjugates (ADC) have been favored by domestic and foreign pharmaceutical industry for its specificity and high efficiency. However, its complex structure, composed of antibody, drug and linker, makes it difficult to predict the druggability of ADC and further leads to the withdrawl of Mylotarg from market. The druggability of ADC will be affected once the characteristics of antibody, drug and linker result in the change of ADC’s pharmacokinetics and pharmacodynamics. As there is few studies on the connection between factors above and ADC druggability, researchers are supposed to look into the mechanism of ADC activities, to dig out the deep-seated key factors (e.g., rate of internalization, drug release rate) that are directly related with ADC activities. Our group has shown that cell metabolic kinetics of ADC could characterize its final activity, and relevant research results have been published in ADVANCED MATERIALS (IF 14.8); thus in this project we intend to further research on the mechanism of how ADC cell metabolic kinetics affect its pharmacodynamics, to grasp the key factors of how ADC exert its activity at the cellular level and animal level, laying a solid foundation for the final evaluation of ADC druggability.