Biotransformation and stability of antibody–drug conjugates: payload metabolism and linker cleavage delineation

“A well-developed bioanalytical strategy is critical in providing key information about the antibody-drug conjugates exposure-response relationship.” Antibody–drug conjugates (ADCs) combine the high potency of cytotoxic drugs and high specificity of monoclonal antibodies to effect elimination of cancer cells in a target-specific manner without the serious side effects of chemotherapeutics [1]. With the recent US FDA approval of Adcetris (brentuximab vedotin) to treat Hodgkin's lymphoma and Kadcyla TM (trastuzumab emtansine) to treat advanced Her2 positive breast cancers, the clinical utility of ADCs is officially recognized. Currently, there are more than 30 ADCs at various stages of clinical trials for a variety...