He Jun, Zeng Xianghua, Wang Chunmei, Wang Enwen, Li Yongsheng
Department of General Surgery Jiande Branch of the Second Affiliated Hospital, School of Medicine, Zhejiang University Jiande Zhejiang China.
Department of Medical Oncology Chongqing University Cancer Hospital Chongqing China.
MedComm (2020). 2024 Jul 28;5(8):e671. doi: 10.1002/mco2.671. eCollection 2024 Aug.
Antibody-drug conjugates (ADCs) consist of monoclonal antibodies that target tumor cells and cytotoxic drugs linked through linkers. By leveraging antibodies' targeting properties, ADCs deliver cytotoxic drugs into tumor cells via endocytosis after identifying the tumor antigen. This precise method aims to kill tumor cells selectively while minimizing harm to normal cells, offering safe and effective therapeutic benefits. Recent years have seen significant progress in antitumor treatment with ADC development, providing patients with new and potent treatment options. With over 300 ADCs explored for various tumor indications and some already approved for clinical use, challenges such as resistance due to factors like antigen expression, ADC processing, and payload have emerged. This review aims to outline the history of ADC development, their structure, mechanism of action, recent composition advancements, target selection, completed and ongoing clinical trials, resistance mechanisms, and intervention strategies. Additionally, it will delve into the potential of ADCs with novel markers, linkers, payloads, and innovative action mechanisms to enhance cancer treatment options. The evolution of ADCs has also led to the emergence of combination therapy as a new therapeutic approach to improve drug efficacy.
抗体药物偶联物(ADCs)由靶向肿瘤细胞的单克隆抗体和通过连接子连接的细胞毒性药物组成。通过利用抗体的靶向特性,ADCs在识别肿瘤抗原后通过内吞作用将细胞毒性药物输送到肿瘤细胞中。这种精确的方法旨在选择性地杀死肿瘤细胞,同时将对正常细胞的损害降至最低,提供安全有效的治疗效果。近年来,随着ADCs的发展,抗肿瘤治疗取得了显著进展,为患者提供了新的有效治疗选择。目前已针对多种肿瘤适应症探索了300多种ADCs,其中一些已获批用于临床,然而,由于抗原表达、ADCs加工和有效载荷等因素导致的耐药性等挑战也随之出现。本综述旨在概述ADCs的发展历程、结构、作用机制、近期成分进展、靶点选择、已完成和正在进行的临床试验、耐药机制及干预策略。此外,还将探讨具有新型标记物、连接子、有效载荷和创新作用机制的ADCs在增强癌症治疗选择方面的潜力。ADCs的发展还催生了联合治疗这一提高药物疗效的新治疗方法。