title: Impact on monoclonal antibody production in murine hybridoma cell cultures of adenosine receptor antagonists and phosphodiesterase inhibitors.
abstract: The effects of different adenosine receptor antagonists and cyclic nucleotide phosphodiesterase (PDE) inhibitors on monoclonal antibody (mAb) titer and cell viability of murine hybridoma cells in culture were measured as part of our investigations to discover additives that enhance mAb production. Specific adenosine receptor antagonists and PDE inhibitors were found to enhance or decrease the titer of immunoglobulin G1 (IgG1) mAbs relative to negative controls, depending on the specific compound and cell line employed. The observed enhancements or decreases in IgG1 mAb titer appeared to be mainly due to an increase or decrease in specific productivity rates (ngmAb/cell), respectively. The different effects of the selective adenosine antagonists suggest that antagonism at the level of the adenosine A2A and A1 or the adenosine A3 receptors result in either enhancement or suppression of IgG1 mAb production by hybridoma cells. Overall, these studies have identified hitherto unknown activities of specific adenosine antagonists and PDE inhibitors which indicate they may have valuable roles as cell culture additives in industrial biomanufacturing processes designed to enhance the yields of mAbs or other recombinant proteins produced by mammalian cell culture procedures.
authors.affiliation: Centre for Green Chemistry, School of Chemistry, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Geoffrey F
authors.initials: GF
authors.lastname: Kelso
authors.affiliation: Centre for Green Chemistry, School of Chemistry, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Shahid A
authors.initials: SA
authors.lastname: Kazi
authors.affiliation: Centre for Green Chemistry, School of Chemistry, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Harris
authors.affiliation: Centre for Green Chemistry, School of Chemistry, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Reinhard I
authors.initials: RI
authors.lastname: Boysen
authors.affiliation: Centre for Green Chemistry, School of Chemistry, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Jamil
authors.initials: J
authors.lastname: Chowdhury
authors.affiliation: Centre for Green Chemistry, School of Chemistry, Monash University, Clayton, Victoria 3800, Australia. Electronic address: milton.hearn@monash.edu.
authors.forename: Milton T W
authors.initials: MTW
authors.lastname: Hearn
mesh_terms: D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000096:biosynthesis* / Q000494:pharmacology; D002110:Caffeine / Q000031:analogs & derivatives / Q000494:pharmacology; D002470:Cell Survival; D006825:Hybridomas; D007074:Immunoglobulin G / Q000096:biosynthesis*; D051379:Mice; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D058915:Purinergic P1 Receptor Antagonists / Q000494:pharmacology*
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D007074:Immunoglobulin G; D010726:Phosphodiesterase Inhibitors; D058915:Purinergic P1 Receptor Antagonists; D002110:Caffeine
keywords: Adenosine antagonist; Hybridoma; Monoclonal antibody; Phosphodiesterase inhibitor