Pilot-scale production of murine monoclonal antibodies in agitated, ceramic-matrix or hollow-fiber cell culture systems.
The purpose of this research was to compare three bioreactor systems for the pilot-scale production of monoclonal antibodies (MAbs). We needed to produce gram quantities of murine MAbs against human prostatic acid phosphatase for use in fragmentation, radiolabeling and in vivo radio-imaging studies. The stable hybridoma cell line secreting IgG1 antibodies was chosen for production. Of the available bioreactor systems, we chose to test an agitating 30-liter bioreactor in repeated batch mode, a ceramic-matrix bioreactor in both repeated batch and continuous perfusion modes and a hollow-fiber bioreactor in continuous perfusion mode. The highest cultured MAb yield, 151 +/- 126 mg/day (mean +/- SD, n = 22), was achieved in the 30-liter bioreactor in repeated batch mode with the MAb being harvested in a large volume of medium, giving a reactor productivity of 4.3 +/ 3.4 mg/liter/day (mean +/- SD, n = 22). The most concentrated MAb was harvested from the continuously perfused hollow-fiber bioreactor, which had the highest reactor productivity, 307 +/ 142 mg/liter/day (mean +/- SD, n = 47) and an average rate of MAb production of 55.3 +/- 25.7 mg/day (mean +/- SD, n = 47). Taking the use of serum into consideration, the cost of MAb production was lowest in the continuously fed and harvested ceramic-matrix and hollow-fiber cell culture systems. A compact blood glucose meter proved to be a novel and suitable device for the rapid monitoring of glucose concentrations in hybridoma cultures.
Kurkela
R
R
Biocenter and Department of Clinical Chemistry, University of Oulu, Finland.
Fraune
E
E
Vihko
P
P
D000135:Acid Phosphatase / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis*; D001769:Blood; D002478:Cells, Cultured; D002516:Ceramics; D003470:Culture Media; D003584:Cytological Techniques; D005947:Glucose / Q000378:metabolism; D006801:Humans; D006825:Hybridomas / Q000276:immunology*; D007700:Kinetics; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008297:Male; D051379:Mice; D011467:Prostate / Q000201:enzymology
D000911:Antibodies, Monoclonal; D003470:Culture Media; D007773:Lactates; D019344:Lactic Acid; D000135:Acid Phosphatase; D005947:Glucose