Antibody-Drug Conjugates: Understanding Associated Drug Design and Pharmacology

Abstract

Antibody-drug conjugates (ADCs) are currently among the fastest growing drug classes in oncology, combining the specificity and targeting capabilities of monoclonal antibodies (mAbs) with the potent cytotoxicity of small molecule drugs. Considered the “biological missiles” of cancer therapy, ADCs are composed of 3 key elements: (1) a mAb framework that selectively binds to an antigen on the tumor cell surface, (2) a cytotoxic drug payload, and (3) a chemical linker attaching the 2 entities. Because each of these components can vary widely among ADCs, the associated drug design is relatively complex, with subtle differences leading to immense diversity in the overall drug structure and associated pharmacological and clinical properties. As medical communication experts, it is essential to have a basic understanding of the various components of ADC design and their potential impact on drug efficacy, safety, and capability in targeting certain degrees of antigen expression and tumor types. This review aims to provide a basic understanding of each component related to ADC design and the role they play in defining the pharmacological properties of a particular ADC.