Optimal and consistent protein glycosylation in mammalian cell culture.
TL;DR: This review will focus on the advancements made in glycosylation control in a manufacturing process, as well as the next steps in understanding and controlling protein glycosYLation.
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Abstract: In the biopharmaceutical industry, mammalian cell culture systems, especially Chinese hamster ovary (CHO) cells, are predominantly used for the production of therapeutic glycoproteins. Glycosylation is a critical protein quality attribute that can modulate the efficacy of a commercial therapeutic glycoprotein. Obtaining a consistent glycoform profile in production is desired due to regulatory concerns because a molecule can be defined by its carbohydrate structures. An optimal profile may involve a spectrum of product glycans that confers a desired therapeutic efficacy, or a homogeneous glycoform profile that can be systemically screened for. Studies have shown some degree of protein glycosylation control in mammalian cell culture, through cellular, media, and process effects. Studies upon our own bioprocesses to produce fusion proteins and monoclonal antibodies have shown an intricate relationship between these variables and the resulting protein quality. Glycosylation optimization will improve therapeutic efficacy and is an ongoing goal for researchers in academia and industry alike. This review will focus on the advancements made in glycosylation control in a manufacturing process, as well as the next steps in understanding and controlling protein glycosylation.
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Citations
The genomic sequence of the Chinese hamster ovary (CHO)-K1 cell line
Xun Xu,Harish Nagarajan,Nathan E. Lewis,Shengkai Pan,Zhiming Cai,Xin Liu,Wenbin Chen,Min Xie,Wenliang Wang,Stephanie Hammond,Mikael Rørdam Andersen,Norma F. Neff,Benedetto Passarelli,Winston Koh,H. Christina Fan,Jianbin Wang,Yaoting Gui,Kelvin H. Lee,Michael J. Betenbaugh,Michael J. Betenbaugh,Stephen R. Quake,Iman Famili,Bernhard O. Palsson,Jun Wang +23 more
TL;DR: A draft genomic sequence of the CHO-K1 ancestral cell line is presented and it is discussed how the availability of this genome sequence may facilitate genome-scale science for the optimization of biopharmaceutical protein production.
Recent Advances in Large-Scale Production of Monoclonal Antibodies and Related Proteins
Abhinav A. Shukla,Jörg Thömmes +1 more
TL;DR: The current state-of-the-art industrial production processes, focusing on downstream technologies, for antibodies and antibody-related products are reviewed and future avenues for evolution are discussed.
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Mammalian cell protein expression for biopharmaceutical production
TL;DR: This review focused on the latest advancements in the field, especially in active areas such as expression systems, glycosylation impact factors, and transient gene expression, which plays more important role in biopharmaceutical early development stages.
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Glycosylation of therapeutic proteins: an effective strategy to optimize efficacy.
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TL;DR: An account of the effects that glycosylation has on the therapeutic efficacy of protein drugs is provided and the current understanding of the mechanisms by which glyCosylation leads to such effects are described.
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TL;DR: The toxicities reported for active and discontinued drugs are important to drive the rational design and improve the therapeutic index of ADCs of the future.
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