PDF(Pubmed)
Abstract：
Antineoplastic therapy is one of the main research themes of this century. Modern approaches have been implemented to target and heighten the effect of cytostatic drugs on tumors and diminish their general/unspecific toxicity. In this context, antibody-drug conjugates (ADCs) represent a promising and successful strategy. The aim of this review was to assess different aspects regarding ADCs. They were presented from a chemical and a pharmacological perspective and aspects like structure, conjugation and development particularities alongside effects, clinical trials, safety issues and perspectives and challenges for future use of these drugs were discussed. Representative examples include but are not limited to the following main structural components of ADCs: monoclonal antibodies (trastuzumab, brentuximab), linkers (pH-sensitive, reduction-sensitive, peptide-based, phosphate-based, and others), and payloads (doxorubicin, emtansine, ravtansine, calicheamicin). Regarding pharmacotherapy success, the high effectiveness expectation associated with ADC treatment is supported by the large number of ongoing clinical trials. Major aspects such as development strategies are first discussed, advantages and disadvantages, safety and efficacy, offering a retrospective insight on the subject. The second part of the review is prospective, focusing on various plans to overcome the previously identified difficulties.
摘要：
抗肿瘤疗法是本世纪的主要研究主题之一。已经实施了现代方法来靶向和增强细胞抑制药物对肿瘤的作用并减少其一般/非特异性毒性。在这种情况下，抗体-药物缀合物(ADC)代表了一种有希望和成功的策略。本次审查的目的是评估有关ADC的不同方面。它们是从化学和药理学的角度以及结构等方面提出的，共轭和发展特殊性以及效应，临床试验,讨论了安全性问题以及未来使用这些药物的前景和挑战.代表性实例包括但不限于以下ADC的主要结构成分：单克隆抗体（曲妥珠单抗，brentuximab),接头（pH敏感，还原敏感，基于肽的，磷酸盐基，和其他)，和有效载荷(多柔比星，emtansine,ravtansine,卡利车霉素）。关于药物治疗的成功，大量正在进行的临床试验支持了与ADC治疗相关的高疗效预期.首先讨论了发展战略等主要方面，优点和缺点，安全性和有效性，提供了对这个问题的回顾性见解。第二部分是前瞻性回顾,专注于克服先前确定的困难的各种计划。
