Factors Affecting the Pharmacology of Antibody–Drug Conjugates

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.