title: Human cell lines for biopharmaceutical manufacturing: history, status, and future perspectives.
abstract: Biotherapeutic proteins represent a mainstay of treatment for a multitude of conditions, for example, autoimmune disorders, hematologic disorders, hormonal dysregulation, cancers, infectious diseases and genetic disorders. The technologies behind their production have changed substantially since biotherapeutic proteins were first approved in the 1980s. Although most biotherapeutic proteins developed to date have been produced using the mammalian Chinese hamster ovary and murine myeloma (NS0, Sp2/0) cell lines, there has been a recent shift toward the use of human cell lines. One of the most important advantages of using human cell lines for protein production is the greater likelihood that the resulting recombinant protein will bear post-translational modifications (PTMs) that are consistent with those seen on endogenous human proteins. Although other mammalian cell lines can produce PTMs similar to human cells, they also produce non-human PTMs, such as galactose-α1,3-galactose and N-glycolylneuraminic acid, which are potentially immunogenic. In addition, human cell lines are grown easily in a serum-free suspension culture, reproduce rapidly and have efficient protein production. A possible disadvantage of using human cell lines is the potential for human-specific viral contamination, although this risk can be mitigated with multiple viral inactivation or clearance steps. In addition, while human cell lines are currently widely used for biopharmaceutical research, vaccine production and production of some licensed protein therapeutics, there is a relative paucity of clinical experience with human cell lines because they have only recently begun to be used for the manufacture of proteins (compared with other types of cell lines). With additional research investment, human cell lines may be further optimized for routine commercial production of a broader range of biotherapeutic proteins.
authors.affiliation: a Biogen , Cambridge , MA , USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Dumont
authors.affiliation: a Biogen , Cambridge , MA , USA.
authors.forename: Don
authors.initials: D
authors.lastname: Euwart
authors.affiliation: a Biogen , Cambridge , MA , USA.
authors.forename: Baisong
authors.initials: B
authors.lastname: Mei
authors.affiliation: a Biogen , Cambridge , MA , USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Estes
authors.affiliation: a Biogen , Cambridge , MA , USA.
authors.forename: Rashmi
authors.initials: R
authors.lastname: Kshirsagar
mesh_terms: D000818:Animals; D001688:Biological Products / Q000378:metabolism*; D002460:Cell Line / Q000378:metabolism*; D006801:Humans; D060847:Metabolic Engineering; D011506:Proteins / Q000378:metabolism
chemical_list: D001688:Biological Products; D011506:Proteins
keywords: Cell culture; HEK 293; clotting factor; glycosylation; immunogenicity; monoclonal antibody; post-translational modification; recombinant protein; therapeutic glycoprotein; vaccine