治疗性抗体半衰期研究进展
Advances in Research on Half-Life of Therapeutic Antibodies
吴亚辉 1罗龙龙 2张冉3
作者信息
- 1. 湖南师范大学医学院,湖南长沙 410205;军事科学院军事医学研究院毒物药物研究所重大疫情应急防控药物研究室,北京 100850
- 2. 军事科学院军事医学研究院毒物药物研究所重大疫情应急防控药物研究室,北京 100850
- 3. 湖南师范大学医学院,湖南长沙 410205
- 折叠
摘要
对于治疗性抗体药物来说,半衰期是其重要的一个药代动力学(PK)参数,也是影响其临床应用可行性和实用性的重要因素.临床上常用的治疗性抗体药物主要以免疫球蛋白G(IgG)为主,针对其半衰期改造的研究也在不断创新,目前延长IgG半衰期的策略主要集中在可结晶片段(Fc)区域改造、等电点(pI)改造、糖基化修饰改造、抗原结合部位pH依赖性改造以及抗原结合钙离子依赖性改造等方面.近年来,驼源纳米抗体(Nb)逐渐成为治疗性抗体药物研究的热门领域,作为一种潜力巨大的小分子抗体,延长其半衰期具有重要意义,以蛋白融合、化学修饰、红细胞载体和多价Nb为主的策略被应用到Nb半衰期改造的研究中.通过对延长IgG和Nb半衰期的一些现有策略和方法进行介绍,并简述半衰期改造后的应用现状,以期为更多其他的治疗性抗体半衰期改造的研究提供参考.
Abstract
For therapeutic antibody drugs,half-life is an important pharmacokinetic(PK)parameter and an important factor affecting the feasibility and usefulness of their clinical applications.IgG is the main therapeutic antibody drug commonly used in clinical practice,and research on its half-life modification is also constantly innovating.Currently,strategies to extend the half-life of IgG are mainly focused on crystallizable fragment(Fc)region modification,isoelectric point(pI)modification,glycosylation modification,pH-dependent modification of the antigen binding site and calcium-dependent modification of antigen binding site.In recent years,camel-derived nanobody(Nb)has gradually become a popular area of therapeutic antibody drug research.As a small molecule antibody with great potential,it is important to prolong its half-life,and strategies based on protein fusion,chemical modification,erythrocyte carrier and multivalent Nb have been applied to modify the half-life of Nb.In this paper,some existing strategies and methods for prolonging the half-life of IgG and Nb are introduced,and the application status after half-life modification is briefly described,hoping to provide some reference for more studies on half-life modification of therapeutic antibodies.
关键词
免疫球蛋白G/纳米抗体/半衰期/新生儿Fc受体Key words
IgG/nanobody/half-life/FcRn引用本文复制引用
基金项目
国家自然科学基金(82204262)
国家自然科学基金(kq2014082)
北京市科技新星人才项目(2211100002121020)
北京市科技新星交叉课题(20220484217)
出版年
2024
NETL
NSTL
万方数据