Faculty of Medicine, "Lucian Blaga" University of Sibiu, 550169 Sibiu, Romania.
Faculty of Agriculture Science, Food Industry and Environmental Protection, "Lucian Blaga" University of Sibiu, 550012 Sibiu, Romania.
Int J Mol Sci. 2024 Jun 26;25(13):6969. doi: 10.3390/ijms25136969.
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.
抗肿瘤治疗是本世纪的主要研究课题之一。现代方法已经被用于针对肿瘤并提高细胞抑制剂药物的效果,同时降低其一般/非特异性毒性。在这方面,抗体药物偶联物(ADC)代表了一种有前途且成功的策略。本综述的目的是评估 ADC 的不同方面。从化学和药理学的角度介绍了 ADC,并讨论了它们的结构、缀合和开发特点以及作用、临床试验、安全性问题以及这些药物未来使用的前景和挑战。代表性的例子包括但不限于 ADC 的以下主要结构成分:单克隆抗体(曲妥珠单抗、本妥昔单抗)、连接子(pH 敏感、还原敏感、基于肽、基于磷酸盐等)和有效载荷(多柔比星、恩美曲妥珠单抗、瑞妥昔单抗、卡利昔单抗)。鉴于药物治疗的高成功率,ADC 治疗所带来的高有效性预期得到了大量正在进行的临床试验的支持。首先讨论了开发策略等主要方面,包括优缺点、安全性和疗效,对这一主题进行了回顾性分析。综述的第二部分具有前瞻性,重点关注克服先前确定的困难的各种计划。