Molecular Pharmacology Section, Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Women's Malignancies Branch, Center for Cancer Research and Natural Products Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.
Lancet. 2019 Aug 31;394(10200):793-804. doi: 10.1016/S0140-6736(19)31774-X.
Antibody-drug conjugates (ADCs) are immunoconjugates comprised of a monoclonal antibody tethered to a cytotoxic drug (known as the payload) via a chemical linker. The ADC is designed to selectively deliver the ultratoxic payload directly to the target cancer cells. To date, five ADCs have received market approval and over 100 are being investigated in various stages of clinical development. In this Therapeutics paper, we review recent clinical experience with the approved ADCs and other promising late-stage candidates on the horizon, following an overview of the biology and chemistry of ADCs and how the individual components of an ADC (antibody [or target], linker and conjugation chemistry, and cytotoxic payload) influence its activity. We briefly discuss opportunities for enhancing ADC efficacy, drug resistance, and future perspectives for this novel antibody-based molecular platform, which has great potential to make a paradigm shift in cancer chemotherapy.
抗体药物偶联物 (ADC) 是由通过化学连接子连接到细胞毒性药物（称为有效载荷）的单克隆抗体组成的免疫偶联物。ADC 的设计旨在将超毒性有效载荷选择性地递送至靶癌细胞。迄今为止，已有五种 ADC 获得了市场批准，并且有 100 多种处于不同临床开发阶段的 ADC 正在被研究。在这篇治疗学论文中，我们回顾了已批准的 ADC 以及其他有前途的晚期候选药物的最新临床经验，首先概述了 ADC 的生物学和化学特性，以及 ADC 的各个组成部分（抗体[或靶标]、连接子和缀合化学以及细胞毒性有效载荷）如何影响其活性。我们简要讨论了提高 ADC 疗效、耐药性的机会以及这个新的基于抗体的分子平台的未来展望，该平台有可能彻底改变癌症化疗。
