Abstract
Batch cultures of mouse-mouse hybridoma cell lines were carried out and their growth and production kinetics investigated. Three main cell specific production patterns (expressed as pg IgG/cell x hour) were found, which can be used as a classification system for hybridoma cell lines (groups I–III). Cells showing the highest IgG-production at the beginning of the batch culture (during the lag and the onset of the log-phase) were classified as either group I and II. The difference was that cell lines of group II showed a second high cell specific production at the onset of the stationary and death phases. Cell lines of group III had a quite constant production of antibodies during their growth; but IgG secretion completely stopped after the beginning of the stationary phase. The implications of these three production patterns on the design of a production process are discussed.
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Altshuler GL, Dziewulski DM, Sowek JA and Belfort G (1986) Continuous hybridoma growth and monoclonal antibody production in hollow fiber reactors-separators. Biotechnol. Bioeng. 28: 646–658.
Birch JR, Boraston R, and Wood L (1985) Bulk production of monoclonal antibodies in fermenters. Trends Biotechnol. 3: 162–166.
Birch JR, Thompson PW, Boraston R, Oliver S and Lambert K (1986) The large scale production of monoclonal antibodies in airlift fermenters. Presented at: UMIST Symposium on Process Possibilities for Plant and Animal Cell Cultures, 25th/26th March 1986, Manchester UK.
Bodeus M, Burtonboy G and Bazin H (1985) Rat monoclonal antibodies. IV: Easy method forin vitro production. J. Immunol. Method. 79: 1–6.
Boraston R, Thompson PW, Garland S and Birch JR (1984) Growth and oxygen requirements of antibody producing mouse hybridoma cells in suspension culture. Develop. Biol. Standard 55: 103–111.
Chen TR (1977)In situ detection of mycoplasma contamination in cell cultures by fluorescent Hoechst 33258 stain. Exp. Cell Res. 104: 255–262.
Cieplinski W, Wardwell J and Schink AM (1983) Kinetics of human light chain synthesis by human-mouse myeloma hybrids. Cancer Biochem. Biophys. 7: 1–10.
Emery AN, Lavery M, Williams B and Handa A (1986) Large-scale hybridoma culture. Presented at: UMIST Symposium on Process Possibilities for Plant and Animal Cell Cultures, 25th/26th March 1986, Manchester, UK.
Emery AN (1986) Growth of hybridomas and secretion of monoclonal antibodiesin vitro. Presented at: The Society of Chemical Industry Symposium on Large-Scale Production of Monoclonal Antibodies, 9th December 1986, London, UK.
Fazekas de St. Groth S (1983) Automated production of monoclonal antibodies in a cytostat. J. Immunol. Method. 57: 121–136.
Köhler G and Milstein C (1975) Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256: 495–497.
Lavery M, Kearns MJ, Price DG, Emery AN, Jefferis R and Nienow AW (1985) Physical conditions during batch culture of hybridomas in laboratory scale stirred tank reactors. Develop. Biol. Standard. 60: 199–206.
Low K and Harbour C (1985) Growth kinetics of hybridoma cells: (1) The effects of varying foetal calf serum levels. Develop. biol. Standard. 60: 17–24.
Merten O-W (1986) The use of different types of fermentor for the production of monoclonal antibodies. Presented at 2nd European Symposium on Protein Purification Technologies, 29th September — 2nd October 1986, Nancy France.
Merten O-W, Reiter S, Himmler G, Scheirer W and Katinger H (1985a) Production kinetics of monoclonal antibodies. Develop. Biol. Standard. 60: 219–227.
Merten O-W, Reiter S and Katinger H (1985b) Stabilizing effect of reduced cultivation temperature on human-mouse hybridomas. Develop. Biol. Standard. 60: 509–512.
Merten O-W, Palfi GE, Klement G and Steindl F (1987) Specific kinetic patterns of production of monoclonal antibodies in batch cultures and consequences on fermentation processes. Presented at 8th ESACT-meeting—32nd Oholo Biological Conference on Modern Approaches to Animal Cell Technology, 6th–10th April 1987, Tiberias II.
Reuveny S, Velez D, Riske F, Macmillan JD and Miller L (1985) Production of monoclonal antibodies in culture. Develop. Biol. Standard. 60: 185–197.
Reuveny S, Velez D, Miller L and Macmillan JD (1986a) Comparison of cell propagation methods for their effect on monoclonal antibodies yield in fermenters. J. Immunol. Method. 86: 61–69.
Reuveny S, Velez D, Macmillan JD and Miller L (1986b) Factors affecting cell growth and monoclonal antibody production in stirred reactors. J. Immunol. Method. 86: 53–59.
Seaver S, Rudolph JL, Ducibella T and Gabriels JE (1984) Hybridoma cell metabolism/antibody secretion in culture. Presented at Biotech '84 USA, In: Online Publications, pp. 325–345, Pinner UK.
Van Wezel AL, Van derVelden-de Groot CAM, DeHaan HH, Van den Heuvel N and Schasfoort R (1985) Large scale animal cell cultivation for production of cellular biologicals. Develop. Biol. Standard. 60: 229–236.
Velez D, Reuveny S, Miller L and Macmillan JD (1986) Kinetics of monoclonal antibody production in low serum growth medium. J. Immunol. Method. 86: 45–52.
Williams JA (1984) Effects of medium concentration on antibody production. J. Tissue Culture Methods 8: 115–118.
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Merten, OW. Batch production and growth kinetics of hybridomas. Cytotechnology 1, 113–121 (1988). https://doi.org/10.1007/BF00146811
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DOI: https://doi.org/10.1007/BF00146811