Systematic fractionation of oligosaccharides of human immunoglobulin G by serial affinity chromatography on immobilized lectin columns

Harada, Hiroshi; Kamei, Masugu; Tokumoto, Yuko; Yui, Seiko; Koyama, Fumihiro; Kochibe, Naohisa; Endo, Tamao; Kobata, Akira

doi:10.1016/0003-2697(87)90507-0

Cited by 97 publications

(45 citation statements)

References 13 publications

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“…Nonfucosylated IgG1 is a normal component of natural human serum IgG (24,25) and is proven to have greatly enhanced ADCC than fucosylated IgG1 through its improved FcgRIIIa binding in vitro (13 -16, 27 -29, 45) and in vivo in a human PBMC-engrafted mouse model (46). In the current study, we further investigated the ADCC of nonfucosylated IgG1 using a human ex vivo model (22,34) by monitoring rituximab-induced B-cell depletion from human whole blood.…”

Section: Discussionmentioning

confidence: 99%

Nonfucosylated Therapeutic IgG1 Antibody Can Evade the Inhibitory Effect of Serum Immunoglobulin G on Antibody-Dependent Cellular Cytotoxicity through its High Binding to FcγRIIIa

Iida

Misaka

Inoue

et al. 2006

Clinical Cancer Research

195

148

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Purpose: Recent studies have revealed that fucosylated therapeutic IgG1s need high concentrations to compensate for FcgRIIIa-competitive inhibition of antibody-dependent cellular cytotoxicity (ADCC) by endogenous human plasma IgG. Here, we investigated whether ADCC of nonfucosylated therapeutic IgG1 is also influenced by plasma IgG in the same way as fucosylated IgG1s. Experimental Design: Ex vivo ADCC upon CD20 + human B cells was induced by incubation of human whole blood with nonfucosylated and/or fucosylated anti-CD20 IgG1s rituximab, and quantified by measuring the remaining CD19 + human B cells using flow cytometry. Results: Nonfucosylated anti-CD20 showed markedly higher (over 100-fold based on EC 50 ) ex vivo B-cell depletion activity than its fucosylated counterpart in the presence of plasma IgG. The efficacy of fucosylated anti-CD20 was greatly diminished in plasma, resulting in the need for a high concentration (over 1.0 Ag/mL) to achieve saturated efficacy. In contrast, nonfucosylated anti-CD20 reached saturated ADCC at lower concentrations (0.01-0.1 Ag/mL) with much higher efficacy than fucosylated anti-CD20 in all nine donors through improved FcgRIIIa binding. Noteworthy, the high efficacy of nonfucosylated anti-CD20 was inhibited by addition of fucosylated anti-CD20. Thus, the efficacy of a 1:9 mixture (10 Ag/mL) of nonfucosylated and fucosylated anti-CD20s was inferior to that of a 1,000-fold dilution (0.01 Ag/mL) of nonfucosylated anti-CD20 alone. Conclusions: Our data showed that nonfucosylated IgG1, not including fucosylated counterparts, can evade the inhibitory effect of plasma IgG on ADCC through its high FcgRIIIa binding. Hence, nonfucosylated IgG1exhibits strong therapeutic potential through dramatically enhanced ADCC at low doses in humans in vivo.

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Section: Discussionmentioning

confidence: 99%

Nonfucosylated Therapeutic IgG1 Antibody Can Evade the Inhibitory Effect of Serum Immunoglobulin G on Antibody-Dependent Cellular Cytotoxicity through its High Binding to FcγRIIIa

Iida

Misaka

Inoue

et al. 2006

Clinical Cancer Research

195

148

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“…Monoclonal immunoglobulin light chains are highly glycosylated (13,36). The molar ratio between basic and neutral sugars vs acid residues is not constant in myeloma immunoglobulins (37,38), whereas this ratio is approximately 76:24 for normal immunoglobulins (39). In spite of advances in the analysis of glycoprotein-associated oligosaccharides (40), there are no reports in the literature about the relationship of tissue distribution to exposed carbohydrate residues.…”

Section: Discussionmentioning

confidence: 99%

The renal and hepatic distribution of Bence Jones proteins depends on glycosylation: a scintigraphic study in rats

Prado¹,

Nicastri²,

Costa³

et al. 1997

Braz J Med Biol Res

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The aim of the present study was to evaluate renal and liver distribution of two monoclonal immunoglobulin light chains. The chains were purified individually from the urine of patients with multiple myeloma and characterized as lambda light chains with a molecular mass of 28 kDa. They were named BJg (high amount of galactose residues exposed) and BJs (sialic acid residues exposed) on the basis of carbohydrate content. A scintigraphic study was performed on male Wistar rats weighing 250 g for 60 min after iv administration of 1 mg of each protein (7.4 MBq), as the intact proteins and also after carbohydrate oxidation. Images were obtained with a Siemens gamma camera with a high-resolution collimator and processed with a MicroDelta system. Hepatic and renal distribution were established and are reported as percent of injected dose. Liver uptake of BJg was significantly higher than liver uptake of BJs (94.3 vs 81.4%) (P<0.05). This contributed to its greater removal from the intravascular compartment, and consequently lower kidney accumulation of BJg in comparison to BJs (5.7 vs 18.6%) (P<0.05). After carbohydrate oxidation, there was a decrease in hepatic accumulation of both proteins and consequently a higher renal overload. The tissue distribution of periodate-treated BJg was similar to that of native BJs: 82.7 vs 81.4% in the liver and 17.3 vs 18.6% in the kidneys. These observations indicate the important role of sugar residues of Bence Jones proteins for their recognition by specific membrane receptors, which leads to differential tissue accumulation and possible toxicity.

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“…No oligosaccharide structures containing sialic acids or bisecting GlcNAc were observed attached to N-glycans from the IgG of the murine NS/O (41) or insect cells in this study. Some sialylation is common for most mammalian-derived N-glycans from IgG, although the level of sialylation and galactosylation can depend on the particular IgG considered (42)(43)(44)(45). The sialylation of an N-linked oligosaccharide from human chimeric IgG 3 produced in Chinese hamster ovary cells increased from 5 to 75% by mutating amino acid 243 from phenylalanine to alanine (46).…”

Section: Comparison Of Hplc Oligosaccharide Profiles In the Presence mentioning

confidence: 99%

Differential N-Glycan Patterns of Secreted and Intracellular IgG Produced in Trichoplusia ni Cells

Hsu

Takahashi

Tsukamoto

et al. 1997

Journal of Biological Chemistry

113

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Insect cells have been widely utilized as hosts for the production of numerous glycoproteins through the baculovirus expression system (1, 2). Native insect cell glycoproteins also serve as models for developmental processes in eucaryotes (3, 4). While the structure, synthesis, and function of oligosaccharides in mammalian glycoproteins are well characterized, information on the carbohydrate structures and processing pathways present in insect cells is limited and sometimes contradictory (5-7). The oligosaccharides in glycoproteins can play critical roles in cellular targeting, structural stability, resistance to proteolysis, immunogenicity, and circulatory halflife (8, 9). With insects representing more than half of the animal species classified (5), there is a need to obtain more information on the carbohydrate structures and processing of glycoproteins from insect cells.Many initial studies of N-glycans in insect cell-derived heterologous glycoproteins indicated the presence of only high mannose-type or short truncated, paucimannosidic oligosaccharides, 1 sometimes containing L-fucosyl 2 residues (6, 7). These observations confirmed the earlier studies of endogenous insect cell glycoproteins which were similarly found to lack complex carbohydrate structures (10 -12). It was presumed that insect cells did not possess the capacity to synthesize complex-type oligosaccharides since the levels of sialyl-, galactosyl-, and N-acetylglucosamine transferases were found to be insignificant (12).In contrast, studies with the recombinant human plasminogen indicated that insect cells could synthesize complex Nlinked oligosaccharides (13). Several more recent studies on homologous glycoproteins also have indicated that certain insect cell lines can synthesize hybrid and complex oligosaccharides. Honeybee venom phospholipase A 2 (PLA 2 ) 3 was found to

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Systematic fractionation of oligosaccharides of human immunoglobulin G by serial affinity chromatography on immobilized lectin columns

Cited by 97 publications

References 13 publications

Nonfucosylated Therapeutic IgG1 Antibody Can Evade the Inhibitory Effect of Serum Immunoglobulin G on Antibody-Dependent Cellular Cytotoxicity through its High Binding to FcγRIIIa

Nonfucosylated Therapeutic IgG1 Antibody Can Evade the Inhibitory Effect of Serum Immunoglobulin G on Antibody-Dependent Cellular Cytotoxicity through its High Binding to FcγRIIIa

The renal and hepatic distribution of Bence Jones proteins depends on glycosylation: a scintigraphic study in rats

Differential N-Glycan Patterns of Secreted and Intracellular IgG Produced in Trichoplusia ni Cells

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