title: EB66 cell line, a duck embryonic stem cell-derived substrate for the industrial production of therapeutic monoclonal antibodies with enhanced ADCC activity.
abstract: Monoclonal antibodies (mAbs) represent the fastest growing class of therapeutic proteins. The increasing demand for mAb manufacturing and the associated high production costs call for the pharmaceutical industry to improve its current production processes or develop more efficient alternative production platforms. The experimental control of IgG fucosylation to enhance antibody dependent cell cytotoxicity (ADCC) activity constitutes one of the promising strategies to improve the efficacy of monoclonal antibodies and to potentially reduce the therapeutic cost. We report here that the EB66 cell line derived from duck embryonic stem cells can be efficiently genetically engineered to produce mAbs at yields beyond a 1 g/L, as suspension cells grown in serum-free culture media. EB66 cells display additional attractive grown characteristics such as a very short population doubling time of 12 to 14 hours, a capacity to reach very high cell density (> 30 million cells/mL) and a unique metabolic profile resulting in low ammonium and lactate accumulation and low glutamine consumption, even at high cell densities. Furthermore, mAbs produced on EB66 cells display a naturally reduced fucose content resulting in strongly enhanced ADCC activity. The EB66 cells have therefore the potential to evolve as a novel cellular platform for the production of high potency therapeutic antibodies.
authors.affiliation: VIVALIS;France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Olivier
authors.affiliation: VIVALIS;France.
authors.forename: Marine
authors.initials: M
authors.lastname: Jacoby
authors.affiliation: VIVALIS;France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Brillon
authors.affiliation: VIVALIS;France.
authors.forename: Sylvana
authors.initials: S
authors.lastname: Bouletreau
authors.affiliation: VIVALIS;France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Mollet
authors.affiliation: VIVALIS;France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Nerriere
authors.affiliation: VIVALIS;France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Angel
authors.affiliation: VIVALIS;France.
authors.forename: Sévérine
authors.initials: S
authors.lastname: Danet
authors.affiliation: VIVALIS;France.
authors.forename: Boussad
authors.initials: B
authors.lastname: Souttou
authors.affiliation: VIVALIS;France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Guehenneux
authors.affiliation: Innate-Pharma; France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Gauthier
authors.affiliation: IRT1 INSERM U892;France.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Berthomé
authors.affiliation: IRT1 INSERM U892;France.
authors.forename: Henri
authors.initials: H
authors.lastname: Vié
authors.affiliation: VIVALIS;France.
authors.forename: Nicola
authors.initials: N
authors.lastname: Beltraminelli
authors.affiliation: VIVALIS;France.
authors.forename: Majid
authors.initials: M
authors.lastname: Mehtali
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000627:therapeutic use*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000235:genetics; D048708:Cell Growth Processes; D002460:Cell Line; D004345:Drug Industry / Q000379:methods*; D004372:Ducks; D053595:Embryonic Stem Cells; D005643:Fucose / Q000737:chemistry* / Q000378:metabolism; D005818:Genetic Engineering; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D058996:Quality Improvement; D013234:Stem Cells / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D005643:Fucose