Control of therapeutic IgG antibodies galactosylation during cultivation process and its impact on IgG1/FcγR interaction and ADCC activity

Simonov, Vladimir; Иванов, С. В.; Smolov, Maxim; Abbasova, S. G.; Piskunov, Aleksandr; Poteryaev, Dmitry

doi:10.1016/j.biologicals.2019.01.002

Cited by 6 publications

(2 citation statements)

References 22 publications

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“…Aside from afucosylation, there is also evidence that terminal galactose residues may also enhance ADCC activity [ 269 ], although not to the same extent as fucose removal [ 282 ]. However, this finding has been questioned [ 283 , 284 ]. More recent evidence suggests that presence of terminal galactose residues enhance the ADCC activity of afucosylated glycan structures, but have no impact when present on fucosylated glycans [ 270 ].…”

Section: Variables Influencing Antibody Effector Functionsmentioning

confidence: 99%

Serum immunoglobulin and the threshold of Fc receptor-mediated immune activation

Bauer-Smith,

Sudol,

Beers

et al. 2023

Biochimica et Biophysica Acta (BBA) - General Subjects

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Section: Variables Influencing Antibody Effector Functionsmentioning

confidence: 99%

Serum immunoglobulin and the threshold of Fc receptor-mediated immune activation

Bauer-Smith,

Sudol,

Beers

et al. 2023

Biochimica et Biophysica Acta (BBA) - General Subjects

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“…one of the critical quality attributes of mAb in terms of pharmaceutical development, because the galactosylation profile affects complement-dependent cytotoxicity [36,37] and antibodydependent cellular cytotoxicity [38][39][40]. Therefore, to adjust mAb activity and maintain consistent quality, galactosylation is often controlled during pharmaceutical process research and development.…”

Section: Plos Onementioning

confidence: 99%

4-(2,5-Dimethyl-1H-pyrrol-1-yl)-N-(2,5-dioxopyrrolidin-1-yl) benzamide improves monoclonal antibody production in a Chinese hamster ovary cell culture

Aki

Katsumata²,

Kakihara³

et al. 2021

PLoS ONE

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There is a continuous demand to improve monoclonal antibody production for medication supply and medical cost reduction. For over 20 years, recombinant Chinese hamster ovary cells have been used as a host in monoclonal antibody production due to robustness, high productivity and ability to produce proteins with ideal glycans. Chemical compounds, such as dimethyl sulfoxide, lithium chloride, and butyric acid, have been shown to improve monoclonal antibody production in mammalian cell cultures. In this study, we aimed to discover new chemical compounds that can improve cell-specific antibody production in recombinant Chinese hamster ovary cells. Out of the 23,227 chemicals screened in this study, 4-(2,5-dimethyl-1H-pyrrol-1-yl)-N-(2,5-dioxopyrrolidin-1-yl) benzamide was found to increase monoclonal antibody production. The compound suppressed cell growth and increased both cell-specific glucose uptake rate and the amount of intracellular adenosine triphosphate during monoclonal antibody production. In addition, the compound also suppressed the galactosylation on a monoclonal antibody, which is a critical quality attribute of therapeutic monoclonal antibodies. Therefore, the compound might also be used to control the level of the galactosylation for the N-linked glycans. Further, the structure-activity relationship study revealed that 2,5-dimethylpyrrole was the most effective partial structure of 4-(2,5-dimethyl-1H-pyrrol-1-yl)-N-(2,5-dioxopyrrolidin-1-yl) benzamide on monoclonal antibody production. Further structural optimization of 2,5-dimethylpyrrole derivatives could lead to improved production and quality control of monoclonal antibodies.

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Recent biopharmaceutical applications of capillary electrophoresis methods on recombinant DNA technology‐based products

et al. 2021

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Recent biopharmaceutical applications of capillary electrophoresis methods on recombinant DNA technology-based productsBiopharmaceuticals (recombinant technology-based products, vaccines, whole blood and blood components, gene therapy, cells, tissues, etc.,) are described as biological medical products produced from various living sources such as human, microbial, animal, and so on by manufacturing, extraction, or semi-synthesis. They are complex molecules having high molecular weights. For their safety and efficacy, their structural, clinical, physicochemical, and chemical features must be carefully controlled, and they must be well characterized by analytical techniques before the approval of the final product. Capillary electrophoresis (CE) having versatile modes can provide valuable safety and efficacy information, such as amino acid sequence, size variants (low and high molecular weight variants), charged variants (acidic and basic impurities), aggregates, N-linked glycosylation, and O-linked glycosylation. There are numerous applications of CE in the literature. In this review, the most significant and recent studies on the analysis of recombinant DNA technology-based products using different CE modes in the last ten years have been overviewed. It was seen that the researches mostly focus on the analysis of mAbs and IgG. In addition, in recent years, researchers have started to prefer CE combined mass spectrometry (MS) techniques to provide a more detailed characterization for protein and peptide fragments.

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Control of therapeutic IgG antibodies galactosylation during cultivation process and its impact on IgG1/FcγR interaction and ADCC activity

Cited by 6 publications

References 22 publications

Serum immunoglobulin and the threshold of Fc receptor-mediated immune activation

Serum immunoglobulin and the threshold of Fc receptor-mediated immune activation

4-(2,5-Dimethyl-1H-pyrrol-1-yl)-N-(2,5-dioxopyrrolidin-1-yl) benzamide improves monoclonal antibody production in a Chinese hamster ovary cell culture

Recent biopharmaceutical applications of capillary electrophoresis methods on recombinant DNA technology‐based products

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