Enhanced Fc-dependent cellular cytotoxicity of Fc fusion proteins derived from TNF receptor II and LFA-3 by fucose removal from Asn-linked oligosaccharides.

Fucose removal from complex-type oligosaccharide of human IgGs results in a major enhancement of Fc-dependent cellular cytotoxicity. The aim of this study was to determine the effect of fucose removal on the effector function of another class of clinically important molecules that can effect cellular cytotoxicity, Fc fusion proteins. The receptors chosen for study were TNF receptor II and LFA-3, both of which have therapeutic significance.

Fucose removal from complex-type oligosaccharide enhances the antibody-dependent cellular cytotoxicity of single-gene-encoded bispecific antibody comprising of two single-chain antibodies linked to the antibody constant region.

Bispecific antibodies (bsAbs) have the potential to extend binding selectivity, increase avidity and exert potent cytotoxicity due to the combination of dual specificities. scFv2-Fc type of single-gene-encoded bispecific antibody, composed of two different single-chain Fvs and an Fc, has been reported to be capable of binding to different antigens. The aim of this study was to determine the effect of fucose removal on effector functions of scFv2-Fc since fucose depletion from oligosaccharide of human IgG1 and scFv-Fc results in significant enhancement of ADCC.

Fucose removal from complex-type oligosaccharide enhances the antibody-dependent cellular cytotoxicity of single-gene-encoded antibody comprising a single-chain antibody linked the antibody constant region.

Fucose removal from complex-type oligosaccharide of human IgG1-type antibody results in a great enhancement of antibody-dependent cellular cytotoxicity (ADCC). The aim of this study was to clarify the effect of fucose removal on effector functions of a single-gene-encoded antibody with an scFv used as the binding domain. We generated both a fucose-negative anti-tumor associated glycoprotein (TAG)-72 scFv-Fc using alpha-1,6-fucosyltransferase knock-out CHO cells and a highly fucosylated scFv-Fc from parental CHO cells.

Fucose depletion from human IgG1 oligosaccharide enhances binding enthalpy and association rate between IgG1 and FcgammaRIIIa.

Depletion of fucose from human IgG1 oligosaccharide improves its affinity for Fcgamma receptor IIIa (FcgammaRIIIa). This is the first case where a glycoform modification is shown to improve glycoprotein affinity for the receptors without carbohydrate-binding capacity, suggesting a novel glyco-engineering strategy to improve ligand-receptor binding. To address the mechanisms of affinity improvement by the fucose depletion, we used isothermal titration calorimetry (ITC) and biosensor analysis with surface plasmon resonance.

Defucosylated chimeric anti-CC chemokine receptor 4 IgG1 with enhanced antibody-dependent cellular cytotoxicity shows potent therapeutic activity to T-cell leukemia and lymphoma.

Human IgG1 antibodies with low fucose contents in their asparagine-linked oligosaccharides have been shown recently to exhibit potent antibody-dependent cellular cytotoxicity (ADCC) in vitro. To additionally investigate the efficacy of the human IgG1 with enhanced ADCC, we generated the defucosylated chimeric anti-CC chemokine receptor 4 (CCR4) IgG1 antibody KM2760. KM2760 exhibited much higher ADCC using human peripheral blood mononuclear cells (PBMCs) as effector cells compared with the highly fucosylated, but otherwise identical IgG1, KM3060.

The absence of fucose but not the presence of galactose or bisecting N-acetylglucosamine of human IgG1 complex-type oligosaccharides shows the critical role of enhancing antibody-dependent cellular cytotoxicity.

An anti-human interleukin 5 receptor (hIL-5R) humanized immunoglobulin G1 (IgG1) and an anti-CD20 chimeric IgG1 produced by rat hybridoma YB2/0 cell lines showed more than 50-fold higher antibody-dependent cellular cytotoxicity (ADCC) using purified human peripheral blood mononuclear cells as effector than those produced by Chinese hamster ovary (CHO) cell lines. Monosaccharide composition and oligosaccharide profiling analysis showed that low fucose (Fuc) content of complex-type oligosaccharides was characteristic in YB2/0-produced IgG1s compared with high Fuc content of CHO-produced IgG1s. YB2/0-produced anti-hIL-5R IgG1 was subjected to Lens culinaris aggulutin affinity column and fractionated based on the contents of Fuc.