Understanding of pharmacokinetic study of antibody drug conjugates

Antibody drug conjugate (ADC) therapeutics utilized the specificity of monoclonal antibodies (mAbs) and potency of highly toxic small molecules. ADCs are typically composed of an mAb with a cytotoxin conjugated to it, resulting in a new eterogeneous mixture of mAb with various numbers of toxins. Due to this heterogeneity characterized by the therapeutic drug-to-antibody ratio, the selection of bioanalytical methods used to understand and develop ADCs can be challenging. Since the therapeutic drugs have both large- and small-molecule components, and one can use bioanalytical methods in both spaces. A combination of bioanalytical methods is typically used to understand the ADC in vitro/in vivo, to understand payload delivery to the site of action, and to establish an exposure-response relationship. Therefore, many challenges and opportunities to learn are involved with this approach, including issues related to ADC analysis strategies and application of these methods to ADC development, analytical establishment and validation, preclinical and clinical PK, PK/PD studies. In this paper, we introduced the progress and difficulties on pharmacokinetic studies of the ADC in order to engage researchers to discuss and analyze the issues on ADC pharmacokinetic studies.