Evaluating the impact of cell culture process parameters on monoclonal antibody N-glycosylation

Ivarsson, Mattias E.; Villiger, Thomas K.; Morbidelli, Massimo; Šoóš, Miroslav

doi:10.1016/j.jbiotec.2014.08.026

Cited by 106 publications

(118 citation statements)

References 66 publications

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“…[33] The branching and terminal residue of the N-glycan is influenced by cell culture conditions such as glucose limitation, dissolved oxygen and pH, with the exact effect being dependent on cell line, and glycoprotein. [34,35] The osmotic conditions and mechanical stress in cell culture do not seem to affect the N-glycan structure. [35] For a detailed review on approaches on how to control antibody glycosylation, the reader is encouraged to read the recent review by Sha et al [36] While N-glycosylation is by far the predominant form of glycosylation present in IgG, O-linked glycans can occasionally be found in the hinge region of IgG3.…”

Section: N-glycosylationmentioning

confidence: 99%

“…[34,35] The osmotic conditions and mechanical stress in cell culture do not seem to affect the N-glycan structure. [35] For a detailed review on approaches on how to control antibody glycosylation, the reader is encouraged to read the recent review by Sha et al [36] While N-glycosylation is by far the predominant form of glycosylation present in IgG, O-linked glycans can occasionally be found in the hinge region of IgG3. [37] Core Fucose The presence of core fucose reduces the binding affinity between the IgG Fc region and the FcγRIIIa (CD16) receptor.…”

Section: N-glycosylationmentioning

confidence: 99%

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Microheterogeneity of Recombinant Antibodies: Analytics and Functional Impact

Beyer

Schuster

Jungbauer

et al. 2017

Biotechnology Journal

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Antibodies are typical examples of biopharmaceuticals which are composed of numerous, almost infinite numbers of potential molecular entities called variants or isoforms, which constitute the microheterogeneity of these molecules. These variants are generated during biosynthesis by so‐called posttranslational modification, during purification or upon storage. The variants differ in biological properties such as pharmacodynamic properties, for example, Antibody Dependent Cellular Cytotoxicity, complement activation, and pharmacokinetic properties, for example, serum half‐life and safety. Recent progress in analytical technologies such as various modes of liquid chromatography and mass spectrometry has helped to elucidate the structure of a lot of these variants and their biological properties. In this review the most important modifications (glycosylation, terminal modifications, amino acid side chain modifications, glycation, disulfide bond variants and aggregation) are reviewed and an attempt is made to give an overview on the biological properties, for which the reports are often contradictory. Even though there is a deep understanding of cellular and molecular mechanism of antibody modification and their consequences, the clinical proof of the effects observed in vitro and in vivo is still not fully rendered. For some modifications such as core‐fucosylation of the N‐glycan and aggregation the effects are clear and should be monitored, but with others such as C‐terminal lysine clipping the reports are contradictory. As a consequence it seems too early to tell if any modification can be safely ignored.

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Section: N-glycosylationmentioning

confidence: 99%

Section: N-glycosylationmentioning

confidence: 99%

Microheterogeneity of Recombinant Antibodies: Analytics and Functional Impact

Beyer

Schuster

Jungbauer

et al. 2017

Biotechnology Journal

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“…In addition to the host cell genome, the cell culture process conditions assuring cell growth and protein expression shape the protein quality attributes as well. According to the common phrase 'the process is the product', the metabolism of the cells closely depends on the culture conditions, including the pH 17 , the temperature 49 , the oxygen tension 17 , the CO 2 content in the culture broth 50 , as well as the type of process, namely perfusion or fed-batch mode 31 . Different metabolic states, which result from differences in culture parameters, very likely express proteins with altered quality attributes.…”

Section: Cell Culture Process Optimizationmentioning

confidence: 99%

“…More specifically in the case of a monoclonal antibody, the presence of the carbohydrate structure interposed between the CH2 domain is pivotal for effector system interactions 15 . A variety of parameters-the cell line, the culture conditions and the cell culture medium compositionshape recombinant protein quality attributes [16][17][18] . The environment that surrounds the cell while in suspension, namely the cell culture medium, plays a key role in the cell metabolism, and for this reason, media design lends itself to alter the key quality attributes of the molecule Introduction within the potential of a given cell line [19][20][21][22] .…”

Section: Introductionmentioning

confidence: 99%

“…The cell line, the culture conditions and the medium composition affect recombinant protein quality attributes 7,17,45 . With respect to cell-line engineering, opting for media optimization considerably reduces development timelines and the complexity of product quality comparability considerations, which typically results from redevelopment of cell lines.…”

Section: Introductionmentioning

confidence: 99%

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Tailoring recombinant protein quality by rational media design

Brühlmann

Jordan

Hemberger³

et al. 2015

Biotechnology Progress

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Clinical efficacy and safety of recombinant proteins are closely associated with their structural characteristics. The major quality attributes comprise glycosylation, charge variants (oxidation, deamidation, and C‐ & N‐terminal modifications), aggregates, low‐molecular‐weight species (LMW), and misincorporation of amino acids in the protein backbone. Cell culture media design has a great potential to modulate these quality attributes due to the vital role of medium in mammalian cell culture. The purpose of this review is to provide an overview of the way both classical cell culture medium components and novel supplements affect the quality attributes of recombinant therapeutic proteins expressed in mammalian hosts, allowing rational and high‐throughput optimization of mammalian cell culture media. A selection of specific and/or potent inhibitors and activators of oligosaccharide processing as well as components affecting multiple quality attributes are presented. Extensive research efforts in this field show the feasibility of quality engineering through media design, allowing to significantly modulate the protein function. © 2015 American Institute of Chemical Engineers Biotechnol. Prog., 31:615–629, 2015

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Multivariate Modeling for Bioreactor Monitoring and Control

Glassey

2016

Bioreactors

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Evaluating the impact of cell culture process parameters on monoclonal antibody N-glycosylation

Cited by 106 publications

References 66 publications

Microheterogeneity of Recombinant Antibodies: Analytics and Functional Impact

Microheterogeneity of Recombinant Antibodies: Analytics and Functional Impact

Tailoring recombinant protein quality by rational media design

Multivariate Modeling for Bioreactor Monitoring and Control

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