Fu Ying, Ho Mitchell
Laboratory of Molecular Biology, National Cancer Institute, Bethesda, MD, USA.
Antib Ther. 2018 Sep;1(2):33-43. doi: 10.1093/abt/tby007. Epub 2018 Aug 30.
Currently, four antibody-drug conjugates (ADCs) are approved by the Food and Drug Administration or the European Medicine Agency to treat cancer patients. More than 60 ADCs are in clinical development for cancer therapy. More than 60% of ADCs in clinical trials employ microtubule inhibitors as their payloads. A better understanding of payloads other than microtubule inhibitors, especially DNA-damaging agents, is important for further development of ADCs. In this review, we highlight an emerging trend of using DNA-damaging agents as payloads for ADCs. This review summarizes recent advances in our understanding gained from ongoing clinical studies; it will help to define the utility of DNA-damaging payloads for ADCs as cancer therapeutics. Future directions of the development of ADCs are also discussed, focusing on targeting drug resistance and combination treatment with immunotherapy.
目前，四种抗体药物偶联物（ADC）已获美国食品药品监督管理局或欧洲药品管理局批准用于治疗癌症患者。超过60种ADC正处于癌症治疗的临床开发阶段。超过60%处于临床试验阶段的ADC采用微管抑制剂作为其有效载荷。更好地了解除微管抑制剂之外的有效载荷，尤其是DNA损伤剂，对于ADC的进一步开发至关重要。在本综述中，我们强调了使用DNA损伤剂作为ADC有效载荷的新趋势。本综述总结了从正在进行的临床研究中获得的最新认识进展；这将有助于明确DNA损伤有效载荷作为癌症治疗药物在ADC中的效用。还讨论了ADC未来的发展方向，重点是靶向耐药性以及与免疫疗法的联合治疗。
