Discovery and development of ADCs: obstacles and opportunities

Here we have provided historical perspectives on the development of ADCs and highlighted the obstacles encountered during the development of different ADC generations, which have guided the success of the next-generation of ADCs with improved efficacy and safety. While novel technologies have brought opportunities for the design of better ADC components, several critical problems still remain unsolved for ADCs. We have provided examples to demonstrate how insightful data can be generated to address critical issues faced throughout the discovery and development of ADCs. Utilizing in vitro, preclinical, and clinical data; and employing PK/PD modeling and simulation strategies, pave the way for successful discovery and development of ADCs with acceptable therapeutic-index. ADCs have brought upon a new era of treatment for not only oncology but other diseases as well.