Lucas Andrew T, Robinson Ryan, Schorzman Allison N, Piscitelli Joseph A, Razo Juan F, Zamboni William C
University of North Carolina (UNC), Eshelman School of Pharmacy, Chapel Hill, NC 27599, USA.
Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Antibodies (Basel). 2019 Jan 1;8(1):3. doi: 10.3390/antib8010003.
The rapid advancement in the development of therapeutic proteins, including monoclonal antibodies (mAbs) and antibody-drug conjugates (ADCs), has created a novel mechanism to selectively deliver highly potent cytotoxic agents in the treatment of cancer. These agents provide numerous benefits compared to traditional small molecule drugs, though their clinical use still requires optimization. The pharmacology of mAbs/ADCs is complex and because ADCs are comprised of multiple components, individual agent characteristics and patient variables can affect their disposition. To further improve the clinical use and rational development of these agents, it is imperative to comprehend the complex mechanisms employed by antibody-based agents in traversing numerous biological barriers and how agent/patient factors affect tumor delivery, toxicities, efficacy, and ultimately, biodistribution. This review provides an updated summary of factors known to affect the disposition of mAbs/ADCs in development and in clinical use, as well as how these factors should be considered in the selection and design of preclinical studies of ADC agents in development.
治疗性蛋白质的快速发展，包括单克隆抗体（mAb）和抗体药物偶联物（ADC），创造了一种在癌症治疗中选择性递送高效细胞毒性药物的新机制。与传统小分子药物相比，这些药物具有诸多优势，但其临床应用仍需优化。单克隆抗体/抗体药物偶联物的药理学很复杂，而且由于抗体药物偶联物由多个成分组成，个体药物特性和患者变量会影响它们的处置。为了进一步改善这些药物的临床应用和合理开发，必须了解基于抗体的药物穿越众多生物屏障所采用的复杂机制，以及药物/患者因素如何影响肿瘤递送、毒性、疗效以及最终的生物分布。本综述提供了已知影响单克隆抗体/抗体药物偶联物在研发和临床应用中处置的因素的最新总结，以及在研发中的抗体药物偶联物临床前研究的选择和设计中应如何考虑这些因素。
