Site-Specific Glycan Conjugation Improves Stability and Efficacy of an Antibody–Drug Conjugates Bearing DXd as a Cytotoxic Payload
This study developed a homogeneous ADC via site-specific conjugation of a potent antitumor agent, a camptothecin derivative, to the <i>N</i>-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) <i>in vivo</i>.
Authors
- Wataru Sumiyoshi (ORCID: https://orcid.org/0000-0002-2855-4529)
- Shino Manabe (ORCID: https://orcid.org/0000-0002-2763-1414)
- Asako Hoshinoo
- Takashi Kinoshita (ORCID: https://orcid.org/0000-0002-3468-002X)
- Shogo Iwamoto
- Ai Mitani
- Chihoko Yoshimura
- Shogo Senga (ORCID: https://orcid.org/0009-0006-8355-5416)
- Methanee Hiranyakorn (ORCID: https://orcid.org/0000-0002-6770-3742)
- Hikaru Yarita
- Ryo Takahashi
Institutions
- Kobe Shukugawa Gakuin University (JP)
- Hoshi University (JP)
- Taiho Pharmaceutical (Japan) (JP)
- Maruishi Pharmaceutical (Japan) (JP)
- Ebara (Japan) (JP)
- Tohoku Medical and Pharmaceutical University (JP)
Publication Details
- Journal
- ACS Omega
- Published
- 2026-02-16
- DOI
- https://doi.org/10.1021/acsomega.5c10898
- Primary Topic
- HER2/EGFR in Cancer Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00