Authors
Yaqi Shi, Yan Zhao, Zhi Liu, Fengnan Song, Xu Wang, Caili Luo, Fei Xia, Mengru Lu, Holger Husi, Weihua Meng, Feng Tang, Wei Huang, Wei Shi
Published in
Chembiochem : a European journal of chemical biology. Volume 27. Issue 14. Pages e70484. Jul 29, 2026.
Abstract
The drug-to-antibody ratio (DAR) represents a critical quality attribute for antibody-drug conjugates (ADCs). Conventional site-specific conjugation strategies typically generate ADCs with defined DAR values ranging from 2 to 8. However, for ultrapotent cytotoxic payloads, lower DAR values have been shown to enhance tumor tissue penetration and improve safety profiles. Similarly, in antibody-oligonucleotide conjugates (AOCs), reduced DAR values contribute to optimized pharmacokinetic behavior. Previously, we developed a glycosite-specific ADC construction method, termed DisacLink technology, based on synthetic LacNAc oxazoline derivatives. Building on this platform, we have now designed bis-functionalized drug-linkers that enable the generation of glycosite-specific DAR1 ADCs. This method achieves high conjugation efficiency, demonstrates the applicability to the major human IgG subclasses and commonly used payloads, yielding site-specific conjugates with acceptable homogeneity, favorable thermal and aggregation stability, and potent in vitro and in vivo antitumor activity.
PMID:
42520171
Bibliographic data and abstract were imported from PubMed on 29 Jul 2026.
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