Dextramabs: A Novel Format of Antibody‐Drug Conjugates Featuring a Multivalent Polysaccharide Scaffold. Issue 3 (28th March 2019)

• Record Type: Journal Article
• Authors: Schneider, Hendrik; Deweid, Lukas; Pirzer, Thomas; Yanakieva, Desislava; Englert, Simon; Becker, Bastian; Avrutina, Olga; Kolmar, Harald
• Is Part Of: ChemistryOpen. Volume 8:Issue 3(2019)
• Page Start: 354
• Page End: 357
• Publication Date: 2019-03-28
• Subjects: ADC -- bioconjugation -- dextran modification -- cancer -- drug discovery; Chemistry -- Periodicals; 540; 540.5
• DOI: 10.1002/open.201900066
• Languages: English
• ISSNs: 2191-1363

Abstract

Abstract: Antibody‐drug conjugates (ADCs) are multicomponent biomolecules that have emerged as a powerful tool for targeted tumor therapy. Combining specific binding of an immunoglobulin with toxic properties of a payload, they however often suffer from poor hydrophilicity when loaded with a high amount of toxins. To address these issues simultaneously, we developed dextramabs, a novel class of hybrid antibody‐drug conjugates. In these architectures, the therapeutic antibody trastuzumab is equipped with a multivalent dextran polysaccharide that enables efficient loading with a potent toxin in a controllable fashion. Our modular chemoenzymatic approach provides an access to synthetic dextramabs bearing monomethyl auristatin as releasable cytotoxic cargo. They possess high drug‐to‐antibody ratios, remarkable hydrophilicity, and high toxicity in vitro . Abstract : A winning approach ! A modular chemo‐enzymatic approach yields dextramabs – novel, highly potent antibody‐drug conjugates based on chemically modified dextran.