抗体药物偶联物(ADC)已经成为一种重要的药物类别，它是一种利用抗体的特异性，并结合有治疗作用的小分子治疗剂的药物。 ADC的三个主要组成元件包括：抗体，连接子，和效应分子。早期研发工作多数集中在改善这些效应分子的功能。目前，研发方向开始已集中如何控制连接子/药物在与抗体偶联时的位点和数量，以产生更均匀的ADC。
近日，在《美国药学科学家协会》杂志(The AAPS journal)上发表了一篇综述，对目前广泛使用的偶联方法，以及近期出现的新方法，包括“点击”偶联和酶连接进行了综述。该综述发表于2015年3月。
该综述讨论当前的接头技术，对比了可裂解连接子和不可裂解连接子的性质，并围绕药物治疗总结了ADC的有效载药量的基本属性。此外，还总结了确定ADC的物理化学性质的测定方法，以及获得均匀产品的纯化方法。最后，研究者认为建立一套ADC的元件选择和分析标准，将有利于新型ADC药物的转化，并保证产物的生物有效性。
参考文献：McCombs et al.The AAPS journal 2015;17(2):339-351
英文链接：Antibody drug conjugates: design and selection of linker, payload and conjugation chemistry .
http://link.springer.com/article/10.1208/s12248-014-9710-8
原文摘要：
Antibody drug conjugates: design and selection of linker, payload and conjugation chemistry.
Antibodydrug conjugates (ADCs) have emerged as an important pharmaceutical class of drugs designed to harness the specificity of antibodies with the potency of small molecule therapeutics. The three main components of ADCs are theantibody, the linker, and the payload; the majority of early work focused intensely on improving the functionality of these pieces. Recently, considerable attention has been focused on developing methods to control the site and number of linker/drug conjugated to theantibody, with the aim of producing more homogenous ADCs. In this article, we review popular conjugation methods and highlight recent approaches including "click" conjugation and enzymatic ligation. We discuss current linker technology, contrasting the characteristics of cleavable and non-cleavable linkers, and summarize the essential properties ofADCpayload, centering on chemotherapeutics. In addition, we report on the progress in characterizing to determine physicochemical properties and on advances in purifying to obtain homogenous products. Establishing a set of selection and analytical criteria will facilitate the translation of novel ADCs and ensure the production of effective biosimilars.
