Improvement of Antibody Activity by Controlling Its Dynamics Using the Glycan-Lectin Interaction

Yoshiyuki Manabe; Yuki Iizuka; Ryuku Yamamoto; Keita Ito; Kanae Hatano; Kazuya Kabayama; Koichi Fukase

doi:10.1002/anie.202304779

Improvement of Antibody Activity by Controlling Its Dynamics Using the Glycan-Lectin Interaction

Angew Chem Int Ed Engl. 2023 Jul 24;62(30):e202304779. doi: 10.1002/anie.202304779. Epub 2023 May 8.

Authors

Yoshiyuki Manabe^{1

2}, Yuki Iizuka¹, Ryuku Yamamoto¹, Keita Ito¹, Kanae Hatano¹, Kazuya Kabayama^{1

2}, Koichi Fukase^{1

2}

Affiliations

¹ Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka, 560-0043, Japan.
² Forefront Research Center, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka, 560-0043, Japan.

PMID: 37083035
DOI: 10.1002/anie.202304779

Abstract

Antibody dynamics on membranes, such as endocytosis and clustering, are vital in determining antibody functions. In this study, we demonstrated that glycan conjugation can modulate antibody dynamics through the glycan-lectin interaction to regulate its potency. The anti-HER2 antibody, an anti-breast-cancer antibody, was conjugated with galactose-containing N-glycan, and its internalization was suppressed by interaction with galectin-3, leading to enhanced complement-dependent cytotoxic (CDC) activity. This glycan-antibody conjugate is proposed as a new approach to modulate antibody activity and may provide an alternative strategy for redeveloping antibody drugs that do not exhibit sufficient activity.

Keywords: Antibodies; Complement-Dependent Cytotoxicity (CDC); Endocytosis; Imaging; N-Glycans.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents*
Immunoconjugates*
Lectins
Polysaccharides

Substances

Lectins
Polysaccharides
Antineoplastic Agents
Immunoconjugates