Structural Glycobiology Laboratory, Biocruces Health Research Institute, Barakaldo, Bizkaia 48903, Spain.
VIB Center for Medical Biotechnology, VIB, Zwijnaarde, Technologiepark 71, 9052 Ghent (Zwijnaarde), Belgium; Department of Biochemistry and Microbiology, Ghent University, Technologiepark 71, 9052 Ghent (Zwijnaarde), Belgium.
Biotechnol Adv. 2023 Oct;67:108201. doi: 10.1016/j.biotechadv.2023.108201. Epub 2023 Jun 17.
Antibody based drugs, including IgG monoclonal antibodies, are an expanding class of therapeutics widely employed to treat cancer, autoimmune and infectious diseases. IgG antibodies have a conserved N-glycosylation site at Asn297 that bears complex type N-glycans which, along with other less conserved N- and O-glycosylation sites, fine-tune effector functions, complement activation, and half-life of antibodies. Fucosylation, galactosylation, sialylation, bisection and mannosylation all generate glycoforms that interact in a specific manner with different cellular antibody receptors and are linked to a distinct functional profile. Antibodies, including those employed in clinical settings, are generated with a mixture of glycoforms attached to them, which has an impact on their efficacy, stability and effector functions. It is therefore of great interest to produce antibodies containing only tailored glycoforms with specific effects associated with them. To this end, several antibody engineering strategies have been developed, including the usage of engineered mammalian cell lines, in vitro and in vivo glycoengineering.
抗体药物，包括 IgG 单克隆抗体，是一类广泛应用于治疗癌症、自身免疫性疾病和传染病的治疗方法的不断发展的药物。IgG 抗体在 Asn297 处具有保守的 N-糖基化位点，该位点带有复杂的 N-糖基化，与其他不太保守的 N-和 O-糖基化位点一起，微调效应功能、补体激活和抗体的半衰期。岩藻糖基化、半乳糖基化、唾液酸化、分叉和甘露糖基化都产生了以特定方式与不同细胞抗体受体相互作用的糖型，并与独特的功能特征相关联。包括临床应用中使用的抗体在内，都是通过附着在它们上面的糖型混合物产生的，这会影响它们的疗效、稳定性和效应功能。因此，生产只含有特定效应相关的特定糖型的抗体具有重要意义。为此，已经开发了几种抗体工程策略，包括使用工程化的哺乳动物细胞系、体外和体内糖基工程。
