1. ez-ADiCon: A novel glyco-remodeling based strategy that enables preparation of homogenous antibody-drug conjugates via one-step enzymatic transglycosylation with payload-preloaded bi-antennary glycan complexes.
- Author
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Chon H, Kanamori S, Hibino K, Nagahara T, Suzuki T, Ohara K, and Narumi H
- Subjects
- Antibodies, Monoclonal chemistry, Hydrophobic and Hydrophilic Interactions, Polysaccharides chemistry, Immunoconjugates chemistry, Antineoplastic Agents chemistry
- Abstract
The conserved N-linked glycan at the Fc domain of recombinant monoclonal antibodies is an attractive target for site-specific payload conjugation for preparation of homogenous antibody-drug conjugates (ADCs). Here, we report a novel ADC constructing strategy, named "ez-ADiCon", that is achieved by one-step enzymatic transglycosylation of a payload-preloaded bi-antennary glycan oxazoline onto a deglycosylated antibody. In this method, a mixture of different glycoforms of the Fc-glycan is replaced with a pre-defined payload-linked glycan. Since two payloads are linked on each donor glycan substrate, efficient conjugation results in a highly homogenous ADC with mostly-four drug molecules per antibody, facilitating hydrophobic interaction chromatography analysis and purification. We validated this conjugation strategy using Monomethyl auristatin E (MMAE) and an anti-Human epidermal growth factor receptor 2 (anti-Her2) antibody as the model ADC components and demonstrated its target-specific in vitro cytotoxicity. Our novel conjugation strategy, ez-ADiCon, provides a new approach for the preparation of next generation ADCs., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Hyongi Chon reports a relationship with MicroBiopharm Japan Co Ltd that includes: employment. Satoshi Kanamori reports a relationship with MicroBiopharm Japan Co Ltd that includes: employment. Kazuhiro Hibino reports a relationship with MicroBiopharm Japan Co Ltd that includes: employment. Takashi Nagahara reports a relationship with MicroBiopharm Japan Co Ltd that includes: employment. Tomohiko Suzuki reports a relationship with MicroBiopharm Japan Co Ltd that includes: employment. Keiichiro Ohara reports a relationship with MicroBiopharm Japan Co Ltd that includes: employment. Hideki Narumi reports a relationship with MicroBiopharm Japan Co Ltd that includes: employment. Satoshi Kanamori has patent pending to MicroBiopharm Japan Co Ltd. Kazuhiro Hibino has patent pending to MicroBiopharm Japan Co Ltd. Takashi Nagahara has patent pending to MicroBiopharm Japan Co Ltd. Keiichiro Ohara has patent pending to MicroBiopharm Japan Co Ltd. Hideki Narumi has patent pending to MicroBiopharm Japan Co Ltd., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
- Published
- 2023
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