化学
聚糖
免疫原性
药品
抗体
结合
计算生物学
糖基化
癌症研究
生物化学
药理学
免疫学
糖蛋白
生物
数学分析
数学
医学
作者
Yen‐Pang Hsu,Omar Nourzaie,Ariel E. Tocher,Kavitha Nerella,Grigori Ermakov,Jae-Youn Jung,Alexandra Fowler,Peidong Wu,Umme Ayesa,Aarron Willingham,Maribel Beaumont,Sampat Ingale
标识
DOI:10.1021/acs.bioconjchem.3c00302
摘要
Antibody-drug conjugates (ADCs) have garnered worldwide attention for disease treatment, as they possess high target specificity, a long half-life, and outstanding potency to kill or modulate the functions of targets. FDA approval of multiple ADCs for cancer therapy has generated a strong desire for novel conjugation strategies with high biocompatibility and controllable bioproperties. Herein, we present a bisecting glycan-bridged conjugation strategy that enables site-specific conjugation without the need for the oligosaccharide synthesis and genetic engineering of antibodies. Application of this method is demonstrated by conjugation of anti-HER2 human and mouse IgGs with a cytotoxic drug, monomethyl auristatin E. The glycan bridge showed outstanding stability, and the resulting ADCs eliminated HER2-expressing cancer cells effectively. Moreover, our strategy preserves the feasibility of glycan structure remodeling to fine-tune the immunogenicity and pharmacokinetic properties of ADCs through glycoengineering.
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