Biopharmaceutical benchmarks 2018

Walsh, Gary

doi:10.1038/nbt.4305

Cited by 798 publications

(554 citation statements)

References 15 publications

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“…For example, we could show that Fc fragments containing complex biantennary glycans attached to both the N- and C-terminal ends of the Fc could inhibit influenza A-mediated agglutination of human erythrocytes (24). The aim of the current study was to reveal possible variation in functional glycosylation related to differences in two host cell lines, CHO-K1 and HEK 293-F, particularly as antibodies and Fc fusions are the fastest growing therapeutic class in the pharmaceutical industry (26, 37, 38).…”

Section: Discussionmentioning

confidence: 99%

“…Chinese hamster ovary (CHO) cell-based systems remain by far the most common mammalian cell line used by the pharmaceutical industry; 84% of products are produced in this cell system, and the remaining approved antibodies are produced in either NS0 or Sp2/0 cells (26). Although CHO cells account for the largest number of FDA approved bio-therapeutics (26), they do not express α1,2/3/4 fucosyltransferase and β-1-4-N-acetylglucosaminyl-transferase III, which are enzymes expressed in human cells (27). Furthermore, humans have active α2,6-sialyltransferase.…”

Section: Introductionmentioning

confidence: 99%

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Choice of host cell line is essential for the functional glycosylation of the fragment crystallizable (Fc) region of human IgG1 inhibitors of influenza B viruses

Blundell

Dell

et al. 2019

Preprint

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Antibodies are glycoproteins that carry a conserved N-linked carbohydrate attached to the Fc, whose presence and fine structure profoundly impacts on their in vivo immunogenicity, pharmacokinetics and functional attributes. The host cell line used to produce IgG has a major impact on this glycosylation, as different systems express different glycosylation enzymes and transporters that contribute to the specificity and heterogeneity of the final IgG-Fc glycosylation profile. Here we compare two panels of glycan-adapted IgG1-Fc mutants expressed in either the HEK 293-F or CHO-K1 systems. We show that the types of N-linked glycans between matched pairs of Fc mutants vary significantly, and in particular with respect to sialylation. These cell line effects on glycosylation profoundly influence the ability of the engineered Fcs to interact with either human or pathogen receptors. For example, we describe Fc mutants that potently disrupted influenza B-mediated agglutination of human erythrocytes when expressed in CHO-K1 but not in HEK 293-F cells.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Choice of host cell line is essential for the functional glycosylation of the fragment crystallizable (Fc) region of human IgG1 inhibitors of influenza B viruses

Blundell

Dell

et al. 2019

Preprint

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“…The global biotherapeutics market was valuated at $188 billion USD in 2017 (Walsh, 2018) and continues to grow. Chinese hamster ovary (CHO) cells are the most widely used mammalian production cell line in the biopharmaceutical industry due to their robustness, scalability, ability to generate human‐like posttranslational modifications, and proven regulatory track record (Jayapal, Wlaschin, Hu, & Yap, 2007; Matasci, Hacker, Baldi, & Wurm, 2009; Walsh, 2010; Wurm, 2004).…”

Section: Introductionmentioning

confidence: 99%

Attenuating apoptosis in Chinese hamster ovary cells for improved biopharmaceutical production

Henry

MacDonald

Orellana

et al. 2020

Biotech & Bioengineering

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Chinese hamster ovary (CHO) cells are the predominant host cell line for the production of biopharmaceuticals, a growing industry currently worth more than $188 billion USD in global sales. CHO cells undergo programmed cell death (apoptosis) following different stresses encountered in cell culture, such as substrate limitation, accumulation of toxic by‐products, and mechanical shear, hindering production. Genetic engineering strategies to reduce apoptosis in CHO cells have been investigated with mixed results. In this review, a contemporary understanding of the real complexity of apoptotic mechanisms and signaling pathways is described; followed by an overview of antiapoptotic cell line engineering strategies tested so far in CHO cells.

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“…The number of approved therapeutic proteins, for example, monoclonal antibodies, is continually increasing, making these biopharmaceuticals the fastest growing sector in the pharmaceutical market. [1,2] Additionally, in recent years, the first biosimilar products have penetrated the market, and given that many first-generation biopharmaceutical patents are due to expire, this trend is expected to continue, creating a demand for more productive manufacturing. [3] So far tremendous developments in cell culture and cell line engineering result in titers above 20 g L −1 and masses of 100 kg per batch.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Strong Cation Exchange Macroporous Polymer Cluster for Convective Protein Chromatography

Lorenz

Vogg

Finkelstein

et al. 2019

Macro Materials & Eng

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Alkyne‐terminated polyelectrolytic brushes based on 3‐sulfopropyl methacrylate are synthesized by reversible addition‐fragmentation chain transfer polymerization and subsequently linked to macroporous polymeric microclusters by Cu(I)‐catalyzed azide alkyne cycloaddition. It is shown that a column packed with the obtained material enables convective cation‐exchange chromatography of proteins, exhibiting flow rate independent resolution and dynamic binding capacity (8 mg mL−1). These flow characteristics are similar to those of monoliths and membranes and therefore improve the mass transport of existing chromatography resins used in the downstream process of therapeutic proteins, while the positive aspects of chromatographic beads are maintained, facilitating implementation in well‐developed platform technologies.

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Biopharmaceutical benchmarks 2018

Cited by 798 publications

References 15 publications

Choice of host cell line is essential for the functional glycosylation of the fragment crystallizable (Fc) region of human IgG1 inhibitors of influenza B viruses

Choice of host cell line is essential for the functional glycosylation of the fragment crystallizable (Fc) region of human IgG1 inhibitors of influenza B viruses

Attenuating apoptosis in Chinese hamster ovary cells for improved biopharmaceutical production

Synthesis of Strong Cation Exchange Macroporous Polymer Cluster for Convective Protein Chromatography

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