Self-hydrolyzing maleimides improve the stability and pharmacological properties of antibody-drug conjugates

• Published in: Nature biotechnology Vol. 32; no. 10; pp. 1059 - 1062
• Main Authors: Lyon, Robert P, Setter, Jocelyn R, Bovee, Tim D, Doronina, Svetlana O, Hunter, Joshua H, Anderson, Martha E, Balasubramanian, Cindy L, Duniho, Steven M, Leiske, Chris I, Li, Fu, Senter, Peter D
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.10.2014; Nature Publishing Group
• Subjects: 631/154/152; 692/699/67/1059/602; 82/1; Acids; Agriculture; Animals; Antibodies - chemistry; Antibody-drug conjugates; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Bioinformatics; Biomedical Engineering/Biotechnology; Biomedicine; Biotechnology; Catalysis; Cell Proliferation - drug effects; Drug therapy; Excipients - chemistry; Female; Humans; Hydrogen-Ion Concentration; Hydrolysis; Immunoconjugates - chemistry; Immunoconjugates - pharmacology; letter; Life Sciences; Maleimides - chemistry; Mice; Mice, SCID; Monoclonal antibodies; Pharmacology; Pharmacology, Experimental; Plasma; Tumors; Xenograft Model Antitumor Assays

A new method for linking antibodies to drugs produces conjugates with improved stability and efficacy. Many antibody-drug conjugates (ADCs) are unstable in vivo because they are formed from maleimide-containing components conjugated to reactive thiols. These thiosuccinimide linkages undergo two comp...