小型化抗体偶联药物及类似物的研究进展  

Research Progress of Small-Format Antibody Drug Conjugates and Analogs

作　　者：余悦 陈豫 马宁宁[1] YU Yue;CHEN Yu;MA Ningning(Wuya College of Innovation,Shenyang Pharmaceutical University,Shenyang 110016,China)

机构地区：[1]沈阳药科大学无涯创新学院,辽宁沈阳110016

出　　处：《药学进展》2024年第1期20-30,共11页Progress in Pharmaceutical Sciences

摘　　要：在癌症治疗中,实体瘤的治疗效果一直是医药界关注的热点。临床上用于治疗实体瘤的靶向药物——抗体和抗体偶联药物存在其相对分子质量较大,导致穿透性有限的问题,在实体瘤治疗中无法发挥预期疗效,且由于其在体内的循环时间长,易对肝和其他组织产生脱靶毒性,限制治疗窗。使用小型化的偶联物或类似药物,如抗体片段偶联药物、支架抗体偶联物或多肽偶联物,将有利于药物快速穿透肿瘤组织,使毒素在肿瘤组织内迅速聚集,且相比于传统抗体偶联药物,小型化偶联物通过肾脏代谢比率增加,从而降低药物因长时间体循环导致的不良反应。但是其过短的半衰期会造成进入肿瘤的实际药量减少,因此也衍生出不同半衰期延长方法,以调节药物半衰期,增加药物进入肿瘤组织的总量,提高治疗效果。通过对不同的小片段技术和代表性药物的临床前或临床进展情况进行介绍,以及对其发展方向进行讨论,以期为小型化抗体偶联药物及类似物的研发提供参考。In cancer treatment,the effectiveness of solid tumor treatment has always been a concern in the pharmaceutical industry.Antibodies and antibody-drug conjugates have been clinically used to treat some solid tumors,but their large molecular weights cause limited penetration and thus cannot fully exert the expected efficacy.And because it circulates for a long time in vivo,it can cause toxicity to the liver and other tissues,limit the therapeutic window.Small-format drug conjugates and their analogs,such as antibody fragment drug conjugates,scaffold antibody-drug conjugates,or peptide drug conjugates,can quickly penetrate the tumor and accumulate in the tumor tissue.Compared with traditional antibodydrug conjugates,the renal metabolism rate of small-format drug conjugates increased,enabling rapid metabolism of free drugs in plasma and reducing adverse reactions caused by long-term systemic circulation of drugs.However,its short half-life may reduce the actual amount of drug entering the tumor.Therefore,different half-life extension methods have been derived to adjust the drug half-life,increase the total amount entering the tumor tissue,and improve the therapeutic effect.This review summarizes the preclinical and clinical progress of small-format drug conjugates and their development trend to provide some reference for the development of small-format drug conjugates and their analogs.

关 键 词：抗体偶联药物 多肽偶联药物 抗体片段 半衰期 

分 类 号：R979.1[医药卫生—药品]