Mechanism Study on Enhancing ADCC Effect of Antibody Drugs via Fc Fragment Defucosylation Modification
Main Article Content
Keywords
Fc fragment modification, defucosylation, ADCC, FcγRIIIa, obinutuzumab, glycosylation engineering
Abstract
Antibody drugs specifically recognize tumor antigens through their Fab fragments and bind to Fcγ receptors on the surface of immune effector cells via their Fc fragments, which promotes antibody-dependent cell-mediated cytotoxicity (ADCC) and thus eliminates target cells. Core fucose residues on the N-glycans of the Fc fragment hinder the high-affinity binding between antibodies and FcγRIIIa through a steric hindrance effect. The affinity between antibodies and FcγRIIIa can be increased by 10 to 50 times after fucose removal, and the ADCC effect is significantly enhanced. This paper systematically elaborates on the molecular mechanism by which defucosylation modification enhances ADCC, introduces its technical implementation paths and development history in detail, and verifies the clinical value of this strategy with Obinutuzumab as an example. On this basis, the paper further discusses the clinical benefits and potential risks of defucosylated antibodies, analyzes the impact of FcγR gene polymorphism on therapeutic efficacy, introduces the latest progress of Obinutuzumab in the treatment of lupus nephritis, and looks forward to the application prospects of this technology in the research and development of the next-generation antibody drugs.
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