Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka, 560-0043, Japan.
Forefront Research Center, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka, 560-0043, Japan.
Angew Chem Int Ed Engl. 2023 Jul 24;62(30):e202304779. doi: 10.1002/anie.202304779. Epub 2023 May 8.
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.
抗体在细胞膜上的动力学，如内吞作用和聚集，对于确定抗体的功能至关重要。在这项研究中，我们证明了糖基化修饰可以通过糖-凝集素相互作用调节抗体的动力学，从而调节其效力。抗 HER2 抗体是一种抗乳腺癌抗体，与含有半乳糖的 N-糖基化修饰，其内化作用被与半乳糖凝集素-3 的相互作用所抑制，导致增强的补体依赖性细胞毒性（CDC）活性。这种糖基化抗体缀合物被提出作为一种调节抗体活性的新方法，可能为重新开发不具有足够活性的抗体药物提供一种替代策略。
