title: Production of target-specific recombinant human polyclonal antibodies in mammalian cells.
abstract: We describe the expression and consistent production of a first target-specific recombinant human polyclonal antibody. An anti-Rhesus D recombinant polyclonal antibody, Sym001, comprised of 25 unique human IgG1 antibodies, was produced by the novel Sympress expression technology. This strategy is based on site-specific integration of antibody genes in CHO cells, using the FRT/Flp-In recombinase system. This allows integration of the expression construct at the same genomic site in the host cells, thereby reducing genomic position effects. Different bioreactor batches of Sym001 displayed highly consistent manufacturing yield, antibody composition, binding potency, and functional activity. The results demonstrate that diverse recombinant human polyclonal antibody compositions can be reproducibly generated under conditions directly applicable to industrial manufacturing settings and present a first recombinant polyclonal antibody which could be used for treatment of hemolytic disease of the newborn and/or idiopathic thrombocytopenic purpura.
authors.affiliation: Symphogen A/S, Elektrovej, building 375, 2800 Kgs. Lyngby, Denmark.
authors.forename: Finn C
authors.initials: FC
authors.lastname: Wiberg
authors.forename: Søren K
authors.initials: SK
authors.lastname: Rasmussen
authors.forename: Torben P
authors.initials: TP
authors.lastname: Frandsen
authors.forename: Lone K
authors.initials: LK
authors.lastname: Rasmussen
authors.forename: Kaja
authors.initials: K
authors.lastname: Tengbjerg
authors.forename: Vincent W
authors.initials: VW
authors.lastname: Coljee
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Sharon
authors.forename: Chiou-Ying
authors.initials: CY
authors.lastname: Yang
authors.forename: Søren
authors.initials: S
authors.lastname: Bregenholt
authors.forename: Lars S
authors.initials: LS
authors.lastname: Nielsen
authors.forename: John S
authors.initials: JS
authors.lastname: Haurum
authors.forename: Anne B
authors.initials: AB
authors.lastname: Tolstrup
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology*; D019149:Bioreactors; D016466:CHO Cells; D006224:Cricetinae; D004254:DNA Nucleotidyltransferases; D004912:Erythrocytes / Q000276:immunology; D018390:Gene Targeting; D005818:Genetic Engineering; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D011994:Recombinant Proteins; D004254:DNA Nucleotidyltransferases; C045119:FLP recombinase