A novel pathway for maytansinoid release from thioether linked antibody-drug conjugates (ADCs) under oxidative conditions |
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| Authors: | Fishkin Nathan Maloney Erin K Chari Ravi V J Singh Rajeeva |
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| Affiliation: | ImmunoGen, Inc., 830 Winter Street, Waltham, MA, USA. nfishkin@immunogen.com |
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| Abstract: | ![]()
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 °C). Oxidized thioether-linked AMCs exhibit high, target-specific cytotoxicity toward cancer cells. |
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