Approaches to Improve the Translation of Safety, Pharmacokinetics and Therapeutic Index of ADCs

Antibody–drug conjugates (ADCs) are an important class of cancer therapies. They are complex molecules, comprising an antibody, a cytotoxic payload, and a linker. ADCs intend to confer high specificity by targeting a unique antigen expressed predominately on the surface of the tumor cells than on the normal cells and by releasing the potent cytotoxic drug inside the tumor causing cytotoxic cell death. Despite high specificity to tumor antigens, many ADCs are associated with off-target and on-target off-tumor toxicities, often leading to safety concerns before achieving the desirable clinical efficacy. Therefore, it is crucial to improve the therapeutic index (TI) of ADCs to enable the full potential of this important therapeutic modality.