CHO Cell Lines

Creative Biolabs provides full services of stable CHO cell line development for recombinant proteins production. CHO cell line is the most frequently used mammalian system for biopharmaceutical manufacturing. tPA (tissue plasminogen activator) is the first approval CHO-derived recombinant protein in 1986. Up to now, there have been over 45 biotherapeutics that are produced in CHO system and approved in the United States and Europe, which accounts for >70% of currently approved recombinant proteins. And the biotherapeutic products include monoclonal antibodies, cytokines, enzymes, Fc-fusion proteins, hormons and clotting factors.

(BioProcess, 2014)

CHO has demonstrated several advantages to make them preferred mammalian cell line for biomanufacturing. First, CHO cells are able to adapt and grow in suspension culture which are the most amenable to GMP procedures and large scale culture. Second, CHO cells are capable of growing in serum-free chemically defined media, which allows recombinant proteins to be reproduced by different batches of cultures with better safety and stability profiles. Third, CHO cells have reduced susceptibility to some viral infections. So, there is little risk that human viruses propagate in CHO cells. Historically, CHO cells can reach a high recombinant protein yield and specific productivity due to gene amplification in several systems. Additionally, recombinant proteins produced by CHO cells possess post translational modifications that are compatible and bioactive in humans. These advances and some common features, such as the tolerance to changes in pH, pressure, oxygen level or temperature during manufacturing, all attribute to the extensive used of CHO cells.

There are two kinds of selection systems applied in CHO system: antibiotic selection system and metabolic selection system. Based on which, various CHO derivatives have been established. For metabolic selection, components essential for cellular metabolism are chosen as markers such as DHFR (dihydrofolate reductase) and GS (glutamine synthetase). Specific drugs are used to inhibit selectable enzyme markers: MTX (methotrexate) inhibits DHFR and MSX (methionine sulphoximine) inhibit GS. Currently, most CHO cell line development is based on the two systems. And common derivatives are CHO-K1, CHO-DHB11, CHO-DXB1, CHO-S, CHO-DG44, etc. Creative Biolabs is capable of using lisence cGMP-CHO-S or DG44 cells to develop stable cell lines for research and manufacturing use. And in order to meet different special requirements including glycosylation modification, reengineered cell lines can be designed and established.

Creative Biolabs is capable of providing the following stable cell lines for various proteins expression:

• ➢ CHO cell lines: GS system, DHFR system;
• ➢ BHK cell line;
• ➢ Mouse myeloma cell lines: NS0, SP2/0, etc.
• ➢ Rat myeloma cell lines: YB2/0, etc.
• ➢ Human cell lines: HEK293 and its derivatives, HT-1080, Huh-7, PER.C6 , etc.

References:

1. Jennifer Dumont, et al. Tingfeng Lai, et al. Human cell lines for biopharmaceutical manufacturing: history, status, and future perspectives. Crit Rev Biotechnol. 2015 Sep 18:1-13.
2. Tingfeng Lai, et al. Advances in Mammalian Cell Line Development Technologies for Recombinant Protein Production. Pharmaceuticals (Basel). 2013 Apr 26;6(5):579-603.

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