Lucas Andrew T, Price Lauren S L, Schorzman Allison N, Storrie Mallory, Piscitelli Joseph A, Razo Juan, Zamboni William C
Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
UNC Eshelman School of Pharmacy, Chapel Hill, NC 27599, USA.
Antibodies (Basel). 2018 Feb 7;7(1):10. doi: 10.3390/antib7010010.
Major advances in therapeutic proteins, including antibody-drug conjugates (ADCs), have created revolutionary drug delivery systems in cancer over the past decade. While these immunoconjugate agents provide several advantages compared to their small-molecule counterparts, their clinical use is still in its infancy. The considerations in their development and clinical use are complex, and consist of multiple components and variables that can affect the pharmacologic characteristics. It is critical to understand the mechanisms employed by ADCs in navigating biological barriers and how these factors affect their biodistribution, delivery to tumors, efficacy, and toxicity. Thus, future studies are warranted to better understand the complex pharmacology and interaction between ADC carriers and biological systems, such as the mononuclear phagocyte system (MPS) and tumor microenvironment. This review provides an overview of factors that affect the pharmacologic profiles of ADC therapies that are currently in clinical use and development.
在过去十年中，治疗性蛋白质领域取得了重大进展，包括抗体药物偶联物（ADC），在癌症治疗中创造了革命性的药物递送系统。虽然这些免疫偶联剂与小分子对应物相比具有若干优势，但其临床应用仍处于起步阶段。其研发和临床应用中的考量因素很复杂，由多个可影响药理学特性的成分和变量组成。了解ADC在跨越生物屏障时所采用的机制以及这些因素如何影响其生物分布、肿瘤递送、疗效和毒性至关重要。因此，有必要开展进一步研究，以更好地理解ADC载体与生物系统（如单核吞噬细胞系统（MPS）和肿瘤微环境）之间复杂的药理学及相互作用。本综述概述了影响目前正在临床应用和研发的ADC疗法药理学特征的因素。
