Tumour Targeting Laboratory, Olivia Newton-John Cancer Research Institute, Melbourne, VIC 3084, Australia,
Department of Medical Oncology, Olivia Newton-John Cancer and Wellness Centre, Austin Health, Melbourne, VIC 3084, Australia.
Molecules. 2020 Oct 16;25(20):4764. doi: 10.3390/molecules25204764.
Antibody-drug conjugates (ADCs) are novel drugs that exploit the specificity of a monoclonal antibody (mAb) to reach target antigens expressed on cancer cells for the delivery of a potent cytotoxic payload. ADCs provide a unique opportunity to deliver drugs to tumor cells while minimizing toxicity to normal tissue, achieving wider therapeutic windows and enhanced pharmacokinetic/pharmacodynamic properties. To date, nine ADCs have been approved by the FDA and more than 80 ADCs are under clinical development worldwide. In this paper, we provide an overview of the biology and chemistry of each component of ADC design. We briefly discuss the clinical experience with approved ADCs and the various pathways involved in ADC resistance. We conclude with perspectives about the future development of the next generations of ADCs, including the role of molecular imaging in drug development.
抗体药物偶联物(ADC)是一种新型药物,利用单克隆抗体(mAb)的特异性,将有效细胞毒性药物递送至癌细胞表面表达的靶抗原。ADC 为向肿瘤细胞递药的同时降低对正常组织的毒性提供了一个独特的机会,从而扩大了治疗窗口,增强了药代动力学/药效学特性。迄今为止,FDA 已批准了 9 种 ADC,全球有 80 多种 ADC 正在进行临床开发。本文概述了 ADC 设计的各个组成部分的生物学和化学特性。简要讨论了已批准 ADC 的临床经验以及 ADC 耐药涉及的各种途径。最后,本文对下一代 ADC 的未来发展前景进行了展望,包括分子成像在药物开发中的作用。