Site-Specific Glycan Conjugation Improves Stability and Efficacy of an Antibody–Drug Conjugates Bearing DXd as a Cytotoxic Payload

ACS Omega 2026 Open access

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Authors: Shino Manabe, Shogo Senga, Shogo Iwamoto, Hikaru Yarita, Ryo Takahashi, Ai Mitani, Wataru Sumiyoshi, Asako Hoshinoo, Methanee Hiranyakorn, Takashi Kinoshita, Chihoko Yoshimura
DOI: 10.1021/acsomega.5c10898
Cited by: 2
References: 75

Abstract

High Resolution Image Download MS PowerPoint Slide This study developed a homogeneous ADC via site-specific conjugation of a potent antitumor agent, a camptothecin derivative, to the N -glycan in the Fc domain of an antibody, achieving a drug-to-antibody ratio (DAR) of 4. The resulting glycan-conjugated ADC exhibited improved thermal stability, reduced aggregation, and reduced premature payload release in human plasma. Despite utilizing the same antibody and payload, this glycan-linked ADC outperformed a clinically approved cysteine-conjugated homogeneous ADC (DAR 8) in vivo .

Fields of Study & Subjects

HER2/EGFR in Cancer Research Cell Adhesion Molecules Research Peptidase Inhibition and Analysis

Publication details

Journal / source
ACS Omega
Publisher
American Chemical Society (ACS)
Volume
11
Issue
8
Pages
13459–13472
Publication date
16 February 2026
Language
EN