Methods for the Generation of Single‐Payload Antibody‐Drug Conjugates

Abstract Antibody‐drug conjugates (ADCs) have emerged as a powerful form of targeted therapy that can deliver drugs with a high level of selectivity towards a specific cell type, reducing off‐target effects and increasing the therapeutic window compared to small molecule therapeutics. However, creating ADCs that are stable, homogeneous, and with controlled drug‐to‐antibody ratio (DAR) remains a significant challenge. Whilst a myriad of methods have been reported to generate ADCs with a DAR of 2, 4, and 8, strategies to generate DAR 1 constructs are seldom reported despite the advantages of low drug loading to tune ADC properties or to allow access to antibody‐antibody and antibody‐protein constructs. This concept article highlights the diversity of methods that have been employed to access single‐payload ADCs and explores the outlook for the field.