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双特异性抗体的药动学研究进展
引用本文:曹庆娟, 张亚宁, 李甜甜, 杜娟娟. 双特异性抗体的药动学研究进展[J]. 药学进展, 2021, 45(9): 669-684.
作者姓名:曹庆娟  张亚宁  李甜甜  杜娟娟
作者单位:1.清华大学药学院, 生命有机磷化学教育部重点实验室, 北京 100084
摘    要:
双特异性抗体(BsAb)是指能同时结合相同或不同分子上的2个不同抗原表位的基因工程抗体。目前处于临床试验阶段的BsAb多达百余种,其适应证也涵盖肿瘤、自身免疫系统疾病等多个领域,有着广阔的应用前景。生物技术的高速发展提供了多种构建BsAb的模式,而不同构建模式的BsAb在体内的吸收、分布、代谢、外排的动力学行为和特征不同。深入研究BsAb药动学行为及其影响因素,对BsAb的合理设计有重要指导意义。通过从BsAb的构建模式出发,同时详细比较不同构建模式的BsAb在体内的药动学表现的差异,以期为BsAb药物设计和临床试验进一步提供参考。

关 键 词:双特异性抗体  药动学  抗体工程
收稿时间:2020-05-01

Reaserch Progress of Pharmacokinetics of Bispecific Antibody
CAO Qingjuan, ZHANG Yaning, LI Tiantian, DU Juanjuan. Reaserch Progress of Pharmacokinetics of Bispecific Antibody[J]. Progress in Pharmaceutical Sciences, 2021, 45(9): 669-684.
Authors:CAO Qingjuan  ZHANG Yaning  LI Tiantian  DU Juanjuan
Affiliation:1.School of Pharmaceutical Sciences, MOE Key Laboratory of Bioorganic Phosphorus Chemistry &Chemical Biology, Tsinghua University, Beijing 100084, China
Abstract:
A bispecific antibody (BsAb) is an engineered antibody that simultaneously binds to 2 different epitopes on one or two antigens. Currently, more than 100 bispecific antibodies are under clinical trials with broad therapeutic applications ranging from cancer to autoimmune diseases. Rapid development of biotechnology has generated various formats to construct bispecific antibodies, which exhibit distinct pharmacokinetic (PK) behaviors of absorption, distribution, metabolism and excretion. Therefore, the in-depth study of the PK behaviors is critical for the rational design of bispecific antibodies. This review summarizes the formats and PK performances of the bispecific antibodies currently under clinical trials, aiming to provide reference for the design of bispecific antibody drugs and their clinical trials.
Keywords:bispecific antibody  pharmacokinetics  antibody engineering
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