A novel pathway for maytansinoid release from thioether linked antibody-drug conjugates (ADCs) under oxidative conditions

A novel pathway for ex vivo maytansinoid release from thioether linked antibody maytansinoid conjugates (AMCs) upon incubation in human plasma has been identified. A thioether succinimide-linked AMC can undergo chemical oxidation followed by sulfoxide elimination under mild aqueous conditions (pH 5.5-7.5, 37 degrees C). Oxidized thioether-linked AMCs exhibit high, target-specific cytotoxicity toward cancer cells.