ANIMAL CELL TECHNOLOGY Products of Today, Prospects for Tomorrow · PDF file...

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    Products of Today, Prospects for Tomorrow


    R. E . Spier Department of Microbiology, University of Surrey

    Guildford, Surrey, UK

    J . B. Griffiths PHLS CAMR, Porten, Salisbury, Wilts, UK

    W. Berthold Dr Karl Thomae GmbH, Biberach an der Riss, Germany


    T H E 1 2 t h M E E T I N G

    T T E R W O R T H I Ν Ε Μ Α Ν Ν


    Section 1. Chairman's Statement

    Presence and future of animal cell technology 3

    Section 2. Making and Selecting Recombinant Cell Lines

    Introduction of DNA into mammalian cells 13 A J van der Eb

    Retrotargeting: Use of defective retroviral DNA fragments to improve 24 recombinant protein production in mammalian cells F Μ Wurm, A Johnson, Τ Etcheverry, Y S Lie, and C J Petropoulos

    Receptor-mediated gene delivery into mammalian cells 30 Ε Wagner, Μ Cotten, C Plank, Κ Mechtler, Κ Zatloukal and Μ L Birnstiel

    Improvement of cell lines for large scale mammalian cell culturing 35 Κ Kitano

    Drosophila cell lines as hosts for recombinant protein expression 43 C Cavegn, J Young, Μ Bertrand and A R Bernard

    Immortalised cell lines for virus diagnosis 50 J Clarke, C MacDonald, U Kreuzburg-Duffy and J Β Griffiths

    Selection strategies for highly productive recombinant cell lines 55 Η Ν Brand, S J Froud, Η Κ Metcalfe, A Ο Onadipe, A Shaw and A J Westlake

    Section 3, Cell Line Characterisation

    Population analysis of a recombinant Chinese hamster ovary cell line 63 expressing recombinant human protein cultured in the presence and absence of methotrexate selective pressure Μ S Sinacore, S Brodeur, S Brennan, D Cohen, Μ Fallon and S R Adamson

    Genetic and biochemical analysis of a murine hybridoma in long-term 69 continuous culture A J Racher, G Ν Stacey, Β J Bolton, A Doyle and J Β Griffiths

    DNA fingerprinting as a quality control marker for the genetic stability 76 of production cells I Doherty, Κ Τ Smith and G Μ Lees

  • Analysis of SV40 early region expression in immortalized mouse 80 macrophage cell lines

    U Ch Κ Kreuzburg-Duffy and C MacDonald

    Section 4. Complex Media Formulations Stimulation of murine hybridomas by cytokines 85 J Η Dempsey, D Η Glass and F Β Ward

    The use of 2-hydroxy-2,4,6-cycloheptarin-l-one (tropolone) as a replacement 88 for transferrin Η Metcalfe, R Ρ Field and S J Froud

    Comparison of long R3IGF-1 with insulin in the support of cell growth and 91 recombinant protein expression in CHO cells J Ν Thomas and V Fung

    Development of a hybridoma cloning medium 96 R Weedle, Κ Carroll, Κ Kavanagh, R O'Kennedy and Μ Clynes

    Performance of gamma-irradiated fetal bovine serum in cell culture 99 J D Keathley, D Wyatt, C Μ Williams, R Festen and C Maben

    Low level FCS adaptation and media development for the culture of 102 two hybridoma cell lines producing IgG and IgM monoclonal antibodies A Sanfeliu, Β Damgaard, J J Cairo, C Casas, C Sola and F Gödia

    Improved bioreactor productivity and manufacturing efficiency using liquid 105 medium concentrates D W Jayme, R Μ Fike, J Μ Kubiak and Ρ J Price

    Cell culture raw materials screening by calcein-AM fluorescence using 110 a 96 well plate format Τ Ihrig, Μ Tsao, Μ Hilton, F Jacobson and Μ Β Sliwkowski

    Importance of extra-cellular matrix in the long term anchorage dependent 115 growth of cell line CHO K l Μ Bridges, C Gebert and Ρ Ρ Gray

    Section 5. Protein and or Serum Free Cultures

    Development of serum free media for engineered NSO cell lines 121 C W Buser, R Beaudet, Ν Soohoo and G G Pugh

    Chloresterol: An important additive for serum-free media? 124 Η Büntemeyer, Μ Burg and J Lehmann

    Serum free ultraCULTURE™ medium: an alternative to the instability 127 χ

  • generated by long-term cultivation of mouse hybridomas Ν Kessler, S Bertrand, G Thomas and Μ Aymard

    Investigations of the TSH antibody producing mouse hybridoma cell line under serum-free media condition E-J Schlaeger, Τ Klier and Κ Christensen

    Interferon gamma production in laboratory bioreactor by lens culinaris lectin stimulated human buffy coat using protein free medium Κ Miomir, Β Filipic, C Schmatz, Κ Carlsson, S Zupan, Ρ Vrhovec, Μ Batic and Β Kovac

    Evaluation of CHO cell growth in a protein-free environment D Ε Wyatt

    Inactivation of serum contaminants D Ε Wyatt, J Keathley, C Williams and R Broce

    Adaption of mammalian cells to protein-free growth D Ε Wyatt

    Section 6. Ammonia/GIutamine and Other Inhibitors

    Ammonium ions inhibit cell growth by intracellular formation of UDP-activated hexosamines Τ Ryll and R Wagner

    Influence of the pH on the ammonia sensitivity of a murine hybridoma cell line Lüdemann, R Pörtner and Η Märkl

    The influence of ammonium on t-PA production from Chinese hamster ovary (CHO) cells C Dyring, Η A Hansen and C Emborg

    Detoxification of ammonium in bioreactor cultivations Κ Martinelle and L Häggström

    Influence of lactate and ammonia on the death rate of hybridoma J L Goergen, A Marc and J Μ Engasser

    The effect of glutamine-containing dipeptides on the growth and productivity of a hybridoma A Christie and Μ Butler

    Inhibitory substance(s) secreted in cell culture media of recombinant CHO and a hybridoma cell line


  • S Siwora, Μ Fingberg, Η Büntemeyer and J Lehmann

    Growth of hybridoma cells is inhibited by gangliosides Η Brandt, J Müthing and J Lehmann

    Section 7. Apoptosis and Cell Biology

    Programmed to die: Cell death via apoptosis Τ G Cotter

    Cell death (apoptosis) in cell culture E-J Schlaeger and S D Simpson

    Cell death by necrosis and adoptosis during the culture of commercially important cell lines R Ρ Singh, Μ Al-Rubeai, C D Gregory and A Ν Emery

    Spontaneous apoptosis contributes negatively to the regulation of hybridoma cell viability F Franek

    Metabolic characteristics and specific requests of hybridoma and CHO cell lines Ρ Schorn, W Noe" and W Berthold

    Nature of cell-cell interactions between recombinant CHO cells expressing human interferon gamma S R Coppen, R Newsam, A J Baines and A Τ Bull

    Section 8. Perfusion cultures and segregation methods

    High density insect cell culture for the production of recombinant proteins with the baculovirus expression system V Jäger, Α Kobold, C Könne, S Μ Deutschmann, Ε Grabenhorst, C Karger and Η S Conradt

    The super-spinner: A mass cell culture bioreactor for the C0 2 incubator R Heidemann, U Riese, D Lükemeyer, Η Büntemeyer and J Lehmann

    Continuous suspension CHO cell culture Η Α Hansen and C Emborg

    Progress in animal cell perfusion technology with superspin R Plüss, D Doyen, L van der Pol and J-L Romette

    Production of a recombinant protein in a high density insect cell cytoflow reactor -X Deramoudt, S Monnet, J Ν Rabaud, J-M Qiuot, Μ Cerutti, G Devauchelle and Μ Kaczorek


  • A compact gravitational settling device for cell retention 227 Κ J Thompson and J S Wilson

    Conical bioreactor with internal lamella settler for perfusion culture 230 of suspension cells C Knaack, G Andr6 and C Chavarie

    Lamellar clarifier - a new device for animal cell retention in perfusion 234 culture systems J Stevens, S Eickel and U Onken

    Perfusion culture of suspended CHO cells employing inclined sedimentation 240 J A Searles, Ρ Todd and D S Kompala

    Section 9. Fixed and Fluidized Beds

    Collegenase production by a cell line in collagen microspheres in a 245 fluidized-bed reactor and its modelization Th Marique, ΤΗ Ρ D Blankaert, I Texeira Guerra and J W£renne

    Development of a bioreactor process for recombinant cell lines 248 A J Racher and J Β Griffiths

    Growth and metabolism of CHO-cells in porous glass carriers 252 Ε Lüllau, Μ Biselli and C Wandrey

    Evolution of the capacitance of cytodex 3 microbeads suspended 256 in growth medium

    V Degouys, F D Menozzi, D A Dubois, L Fabry and A Ο A Miller

    Section 10· Porous microcarriers High density culture using macroporous microcarrier 261 J Shirokaze, Μ Nogawa and R Ogura

    Growth of Spodoptera cells on porous microcarriers (Verax) production 264 of recombinant proteins G R Pettman and C J Mannix

    Protein free culture of R-CHO and hybridoma cells and macroporous 267 polypore® carrier G Blüml, Μ Reiter, Ν Zach, Τ Gaida, C Schmatz, A Assadian, Κ Strutzenberger and Η Katinger

    Section 11. Hollow Fibre Bioreactors

    A novel hepatocyte entrapment, hollow fiber bioreactor as a bio-artificial liver 273 Μ V Peshwa, S L Nyberg, F J Wu, Β Amiot, F Β Cerra and W-S Hu


  • Pitfalls of bioprocessing a human monoclonal multireactive IgM antibody U Marx, D Roggenbuck, Μ Wilding, Η Tanzmann and S Jahn


    Hollow fiber cell culture - a proven alternative Β Horweth

    Section 12. Novel Bioreactors


    Development of a new membrane reactor for large scale mammalian cell culture 287 J L Goergen, A Marc, J Μ Engasser, J Ν Rabaud, G Pierry, V Geaugey, I Geahel and J Hache

    A simple magnetic driven mini-reactor for fluidized and packed beds 290 Τ Gaida, W Schich, Μ Reiter, G Blüml, Ν Zach and Η Katinger