Overview of antibody-drug conjugates nonclinical and clinical toxicities and related contributing factors

An antibody-drug conjugate (ADC), consisting of an antibody, a chemical linker, and a payload, can selectively deliver a highly cytotoxic payload to cancer cells and minimize the systemic toxicity of the payload by harnessing the selectivity of the antibody. However, many ADCs have unacceptable toxic effects due to the expression characteristics of target antigens, structural characteristics of antibodies, linker stability and payload properties, which have slowed their development progress. In this review, we describe the effects of the structure of each component of an ADC molecule on its toxicity, explore and discuss the toxicity profiles of various ADCs in the main body tissues/organs by using nonclinical and clinical data obtained from marketed ADCs, aiming to provide a reference for the development of novel ADC molecules and to facilitate related nonclinical and clinical studies.