Exo-Cleavable Linkers: Enhancing Stability and Therapeutic Efficacy in Antibody-Drug Conjugates

Customized drug delivery systems are essential for precision medicine, with antibody-drug conjugates (ADCs) representing a pivotal approach that integrates cytotoxic payloads with monoclonal antibodies (mAbs) through sophisticated chemical linkers. However, optimizing ADC stability while achieving controlled payload release remains challenging. The FDA-approved valine-citrulline (Val-Cit) linker commonly used in ADCs, suffers from issues such as hydrophobicity-induced aggregation, limited drug-antibody ratio (DAR), and premature payload release.