afucosylated

Afucosylated refers to glycoproteins that lack fucose residues on their N-linked glycans, most notably on the Fc region of Immunoglobulin G (IgG). In human IgG, the conserved Fc glycan attached to asparagine 297 normally carries a core fucose; the absence of this core fucose defines afucosylation. Afucosylation can also occur on other glycoproteins, but its effects are best described in the context of IgG.

The presence or absence of core fucose significantly alters receptor interactions. Afucosylated IgG exhibits markedly higher binding affinity to FcγRIIIa (CD16) on natural killer cells and to FcγRIIIb on certain leukocytes, enhancing antibody-dependent cellular cytotoxicity (ADCC). This modification can thus boost the potency of therapeutic antibodies that rely on ADCC for anti-tumor activity. It may also subtly influence interactions with other Fc receptors and the overall effector profile of the antibody.

Production and applications: Afucosylation is leveraged in biotechnology through glycoengineering. Antibodies produced in FUT8-deficient cell lines or subjected to controlled culture conditions yield afucosylated Fc glycans. Therapeutic examples include obinutuzumab (anti-CD20) and mogamulizumab (anti-CCR4), both engineered to enhance ADCC. Analytical methods such as mass spectrometry, high-performance liquid chromatography, and lectin-based assays are used to characterize glycoforms.

Safety and considerations: Increased ADCC potency can improve efficacy but may raise risks of inflammatory or immune-related adverse events. Manufacturing consistency and glycoform heterogeneity are important quality considerations for afucosylated therapeutics.