Antibody-Drug Conjugates and Tissue-Agnostic Drug Development: An Update.

ABSTRACT: Antibody-drug conjugates (ADCs) deliver effective medications to tumor cells that express specific antigens, maximizing efficacy and reducing adverse effects. Because ado-trastuzumab emtansine was approved in 2013, 5 ADCs received US Food and Drug Administration approval for solid tumor treatment. Technical advancements in the development of each component of ADCs allowed novel monoclonal antibodies, linkers, and payloads to increase drug transport to malignant cells and drug activity even in cancers with heterogeneous antigen expression. In addition, several ADCs are in development using new molecular targets expressed across a broad range of histologies to allow the use of ADC biomarker-driven therapy irrespective of the primary tumor site. This suggests that the future efficacy of ADCs in multiple histologies may be similar to other classes of drugs that are considered histology-agnostic therapies nowadays. This review focuses on novel ADCs for the treatment of solid tumors, including topics such as their structure and mechanism of action, the latest indications of already US Food and Drug Administration-approved ADCs, and the outlook for new promising ADCs under development for the treatment of tumors of various histologies.