Review Article

用于癌症靶向的免疫偶联物:抗体-药物偶联物和抗体功能化纳米颗粒的综述。

卷 28, 期 13, 2021

发表于: 25 May, 2020

页: [2485 - 2520] 页: 36

弟呕挨: 10.2174/0929867327666200525161359

价格: $65

摘要

由于减少了副作用并提高了不同类型癌症的总体疗效和生存率,最近已重点研究了靶向治疗。考虑到最近二十年来许多单克隆抗体的批准,可以通过单克隆抗体和小分子化学疗法的组合来完成癌症治疗。因此,在临床上将在单一给药系统中组合两种药物的策略是重要的。在这种情况下,有两种策略是可行的,并将在本综述中进行进一步讨论:抗体-药物偶联物(ADC)和抗体功能化的纳米颗粒。首先,重要的是更好地了解可能用于癌症治疗的分子靶标,研究能够选择性结合抗体的不同抗原。选择最佳靶点后,可以通过将细胞毒性药物与能够靶向癌细胞抗原的抗体连接来制备ADC。简而言之,ADC将由单克隆抗体(MAb),细胞毒性分子(细胞毒素)和化学接头形成。通常,表面暴露的赖氨酸或半胱氨酸残基的硫醇基团用作接头-药物分子的锚定位点。应考虑的另一种策略是抗体功能化的纳米颗粒。基本上,脂质体,聚合物纳米颗粒和无机纳米颗粒可以连接到特异性抗体上进行靶向治疗。可以使用不同的偶联策略,但纳米颗粒可在马来酰亚胺和硫醇化抗体之间偶联,或通过添加乙基-3-(3-二甲基氨基丙基)碳二亚胺(EDC)/ N-羟基琥珀酰亚胺(NHS)(1:5)并进一步添加而激活抗体的使用是一些最常用的策略。在本文中,将介绍和讨论分子靶标和结合策略,以更好地理解所介绍的体外和体内应用。同样,ADC和结合抗体的纳米颗粒的临床开发在临床开发部分中讨论。最后,由于与靶向疗法相关的创新,可以方便地分析对专利和技术的影响。介绍并讨论了与专利数量的时间演变,专利持有人的分布以及与癌症类型相关的专利数量有关的信息。因此,我们的目的是概述针对癌症的免疫偶联物的最新发展,并强调临床相关性和创新性的最重要方面。

关键词: 抗体,药物靶向,癌症,免疫偶联物,纳米颗粒,单克隆抗体。

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