抗体与药物的位点特异性偶联化学方法学研究进展

Research Progress on the Chemical Methods for Site-specific Coupling of Antibodies and Drugs

关键词:  抗体偶联药物|位点特异性|单克隆抗体|化学修饰|靶向治疗

Key words:  antibody drug conjugates|site specificity|monoclonal antibody|chemical modification|targeted therapy

摘要:

发展高效、安全的肿瘤治疗方法是现代医学的主要挑战之一。目前临床上抗体偶联药物(antibody drug conjugates, ADC)已成为肿瘤治疗最有力的工具之一。传统的ADC药物是利用赖氨酸残基作为偶联位点，其偶联具有高度异质性，可能会导致药物可重复性差，治疗指数低下。因此，如何通过位点特异性偶联来规避这些潜在问题是ADC药物研究的重点领域。最近几年，位点特异性的蛋白化学修饰方法领域取得的重大进展，也一定程度上促进了均质ADC药物的合成。因此，本文重点对目前用于构建ADC的位点特异性化学偶联方法进行综述，以期为抗体偶联药物偶联化学的发展提供参考。

Abstract:

One of the main challenges of modern medicine is the development of efficient and safe tumor treatment methods. Antibody drug conjugates(ADC) have clinically become one of the most powerful tools for tumor treatment. Most of coupling strategy of traditional ADC drugs is using the lysine residues as the coupling sites. However, using this strategy may be highly heterogeneous, which may lead to poor drug reproducibility and low therapeutic index. Therefore, how to avoid these potential problems is the key-point of ADC drug research. In recent years, significant advances in the field of site-specific protein chemical modification methods have also partly promoted the synthesis of homogeneous ADC drugs. Therefore, this review focuses on the site-specific chemical coupling methods currently used to construct ADC, in order to provide a reference for the development of antibody-conjugated drug-conjugation chemistry.