Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
J Cell Physiol. 2018 Sep;233(9):6441-6457. doi: 10.1002/jcp.26435. Epub 2018 Mar 25.
Over the recent decades, the use of antibody-drug conjugates (ADCs) has led to a paradigm shift in cancer chemotherapy. Antibody-based treatment of various human tumors has presented dramatic efficacy and is now one of the most promising strategies used for targeted therapy of patients with a variety of malignancies, including hematological cancers and solid tumors. Monoclonal antibodies (mAbs) are able to selectively deliver cytotoxic drugs to tumor cells, which express specific antigens on their surface, and has been suggested as a novel category of agents for use in the development of anticancer targeted therapies. In contrast to conventional treatments that cause damage to healthy tissues, ADCs use mAbs to specifically attach to antigens on the surface of target cells and deliver their cytotoxic payloads. The therapeutic success of future ADCs depends on closely choosing the target antigen, increasing the potency of the cytotoxic cargo, improving the properties of the linker, and reducing drug resistance. If appropriate solutions are presented to address these issues, ADCs will play a more important role in the development of targeted therapeutics against cancer in the next years. We review the design of ADCs, and focus on how ADCs can be exploited to overcome multiple drug resistance (MDR).
在最近几十年,抗体药物偶联物(ADC)的应用带来了癌症化疗的范式转变。基于抗体的各种人类肿瘤治疗方法已经显示出显著的疗效,目前已成为针对包括血液恶性肿瘤和实体瘤在内的多种恶性肿瘤患者的靶向治疗最有前途的策略之一。单克隆抗体(mAb)能够将细胞毒性药物选择性地递送至肿瘤细胞,这些肿瘤细胞表面表达特定的抗原,并且已被提议作为用于开发抗癌靶向治疗的新型药物类别。与对健康组织造成损伤的传统治疗方法不同,ADC 利用 mAb 特异性地附着在靶细胞表面的抗原上,并传递其细胞毒性有效载荷。未来 ADC 的治疗成功取决于密切选择靶抗原、提高细胞毒性有效载荷的效力、改善连接子的性质和降低耐药性。如果提出适当的解决方案来解决这些问题,ADC 将在未来几年的癌症靶向治疗药物的开发中发挥更重要的作用。我们综述了 ADC 的设计,并重点探讨了如何利用 ADC 来克服多药耐药性(MDR)。