title: A novel pathway for maytansinoid release from thioether linked antibody-drug conjugates (ADCs) under oxidative conditions.
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.
authors.affiliation: ImmunoGen, Inc., 830 Winter Street, Waltham, MA, USA. nfishkin@immunogen.com
authors.forename: Nathan
authors.initials: N
authors.lastname: Fishkin
authors.forename: Erin K
authors.initials: EK
authors.lastname: Maloney
authors.forename: Ravi V J
authors.initials: RV
authors.lastname: Chari
authors.forename: Rajeeva
authors.initials: R
authors.lastname: Singh
mesh_terms: D000906:Antibodies / Q000737:chemistry*; D045744:Cell Line, Tumor; D006801:Humans; D006863:Hydrogen-Ion Concentration; D018796:Immunoconjugates / Q000097:blood / Q000737:chemistry* / Q000633:toxicity; D008301:Maleimides / Q000737:chemistry; D008453:Maytansine / Q000737:chemistry*; D010084:Oxidation-Reduction; D011092:Polyethylene Glycols / Q000737:chemistry; D013434:Sulfenic Acids / Q000737:chemistry
chemical_list: D000906:Antibodies; D018796:Immunoconjugates; D008301:Maleimides; D013434:Sulfenic Acids; D008453:Maytansine; D011092:Polyethylene Glycols; C025285:N-(4-carboxycyclohexylmethyl)maleimide N-hydroxysuccinimide ester