天然抗体定点偶联技术的前沿进展

Advances in Site-Specific Conjugation Technologies for Native Antibodies

关键词:  抗体偶联药物  定点偶联  天然抗体  靶向治疗

Key words:  antibody-drug conjugates  site-specific conjugation  native antibody  targeted therapy

摘要:

抗体修饰技术在近年来取得了突破性进展,驱动了抗肿瘤抗体偶联药物(antibody-drug conjugate,ADC)的快速发展。相比于传统的抗体定点偶联技术,在天然抗体上实现精确定点修饰具有各方面的显著优势,比如无需抗体工程改造、定点偶联工序简化等等。本篇文章系统全面地概述了针对天然抗体的定点偶联技术前沿进展,包括邻近修饰、聚糖重塑、链间二硫键桥接、酶促偶联、化学修饰、DNA(脱氧核糖核酸)介导定点偶联等六个大类,介绍分析了AJICAP技术、DTPC技术等多种新兴的ADC偶联技术,以期为下一代抗体偶联技术的开发提供新思路。

Abstract:

Recent breakthroughs in antibody modification technologies have propelled the rapid development of antibody-drug conjugates (ADCs) for cancer treatment. Compared to traditional site-specific conjugation techniques, achieving precise site modifications on natural antibodies offers significant advantages, such as eliminating the need for antibody engineering and simplifying the conjugation process. This article provides a comprehensive overview of the cutting-edge advancements in site-specific conjugation technologies targeting natural antibodies, categorized into six major types: adjacent modification, glycan remodeling, interchain disulfide bridging, enzymatic conjugation, chemical modification, and DNA-mediated site-specific conjugation. It also analyzes various emerging ADC conjugation technologies, including AJICAP and DTPC, with the aim of providing new insights for the development of the next generation of antibody conjugation technologies.