A Decade of Animal Cell Culture: A Crisis Averted As Knowledge Expands

摘要

Eukaryotic cells are fragile and finicky, requiring very specific culture conditions and nutrients to survive, grow, and be productive in an ex vivo environment. Even so, they have become vital to the biopharmaceutical industry's ability to make complex biological products — overtaking yeast as a production system around 1990 and surpassing bacteria in the number of associated product approvals five years later (l). Since then, they have become even more useful, expanding their reach into the vaccine world. Mammalian cell lines — especially Chinese hamster ovary (CHO), NSO, and Sp2/0 myelomas and hybridomas, baby hamster and human embryonic kidney cells (BHK, HEK), and newer proprietary lines such as Crucell's PER.C6 cells — can express correctlyformed proteins with complicated posttranslational modifications that are essential to their biological function. And the baculovirus expression vector system (BEVS) for transient protein expression by insect cells — well established in laboratory settings but slow to be adopted in bioprocessing -— has come into its own as a vaccine production system. New vaccines such as those for human papilloma virus are made using the BEVS, and influenza vaccine makers are transitioning from egg-based productionto mammalian cell culture (2). Transient expression as a concept has even begun to see use with mammalian cells, too.