Baqiyatallah Research Center for Gastroenterology and Liver Diseases (BRCGL), Baqiyatallah University of Medical Sciences, Tehran, Iran.
Department of Nursing, School of Nursing, Larestan University of Medical Sciences, Larestan, Iran.
J Cell Physiol. 2019 May;234(5):5628-5642. doi: 10.1002/jcp.27419. Epub 2018 Nov 27.
Targeted delivery of therapeutic molecules into cancer cells is considered as a promising strategy to tackle cancer. Antibody-drug conjugates (ADCs), in which a monoclonal antibody (mAb) is conjugated to biologically active drugs through chemical linkers, have emerged as a promising class of anticancer treatment agents, being one of the fastest growing fields in cancer therapy. The failure of early ADCs led researchers to explore strategies to develop more effective and improved ADCs with lower levels of unconjugated mAbs and more-stable linkers between the drug and the antibody, which show improved pharmacokinetic properties, therapeutic indexes, and safety profiles. Such improvements resulted in the US Food and Drug Administration approvals of brentuximab vedotin, trastuzumab emtansine, and, more recently, inotuzumab ozogamicin. In addition, recent clinical outcomes have sparked additional interest, which leads to the dramatically increased number of ADCs in clinical development. The present review explores ADCs, their main characteristics, and new research developments, as well as discusses strategies for the selection of the most appropriate target antigens, mAbs, cytotoxic drugs, linkers, and conjugation chemistries.
将治疗分子靶向递送至癌细胞被认为是一种有前途的癌症治疗策略。抗体药物偶联物（ADC）是通过化学连接子将单克隆抗体（mAb）与生物活性药物偶联而成的，已成为一类有前途的抗癌治疗药物，是癌症治疗中发展最快的领域之一。早期 ADC 的失败促使研究人员探索开发更有效和改进的 ADC 的策略，这些 ADC 具有更低水平的未缀合的 mAb 和药物与抗体之间更稳定的连接子，从而表现出改善的药代动力学特性、治疗指数和安全性特征。这些改进导致美国食品和药物管理局批准了 Brentuximab vedotin、Trastuzumab emtansine，以及最近的 Inotuzumab ozogamicin。此外，最近的临床结果引起了更多的关注，这导致了临床开发中 ADC 的数量急剧增加。本综述探讨了 ADC 的主要特征和新的研究进展，并讨论了选择最合适的靶抗原、mAb、细胞毒性药物、连接子和缀合化学的策略。
