Animal Cell Technology: Products from Cells, Cells as Products

Animal Cell Technology: Products from Cells, Cells as Products

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Containing, in the form of concise papers of limited length, the proceedings of the 16th ESACT meeting that was held in Lugano, Switzerland, in April 1999, this text is intended to provide a useful resource of the most up-to-date information in animal cell technology, at least until the next meeting in 2001. Classical approaches for the use of animal cells (for example, production of virus vaccines) remain an important technology. However, it appears that major technological advances and major growth are occurring in other areas. Most importantly, protein production on the basis of recombinant DNA molecules transferred into animal cells appears to be an ever-increasing field of interest and innovation. Increasingly animal cells are being used as substrates for the study of gene activation and repression, and also for the more rapid production of small and moderate quantities of interesting proteins. Tissue engineering, somatic gene/cell therapy, organ-replacement technologies, and cell-based bio-sensors all contribute to a considerable widening of interest and research activity, based on animal cell technology.

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Published 01 January 2000
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CONTENTS
16th ESACT Meeting Organising Committee
xxi
ESACT Executive Committee xxii
Sponsors
Companies Participating in the Trade Exhibition
LIST OF PARTICIPANTS
xxiii
xxiv
xxv
INTRODUCTION Products from Cells - Cellas as Productslxxi
ACKNOWLEDGEMENTSlxxiii
CHAPTER I. Improvement and Induction of High Productivity
Recombinant Pharmaceutical Protein Overexpression in an IRF-I Proliferation Controlled Production System Geserick, C.; Schroeder, K.; Bonarius, H.; Kongerslev, L.; Schlenke, P.; Hauser, H.; Mueller, P.P.
The Real Meaning of High Expression Grammatikos, S.I.; Bergemann, K.; Werz, W.; Brax, I.; Bux, R.; Eberhardt, P.; Fieder, J.; Noé, W.
11
3
A Novel Mammalian Gene Regulation System Responsive to Streptogramin Antibiotics Fussenegger, M.; Von Stockar, B.; Fux, C.; Rimann, R.; Morris, R.; Thompson, C.J.; Bailey, J.E. 19
Feedback Control of Redox Potential in Hybridoma Cell Culture Meneses, A.; Gomez, A.; Ramirez, O.T. 23
Genetic manipulation of the Protein Synthetic Capacity of Mammalian Cells Heaton, M.; Birch, J.; Hovey, A.; Kallmeier, R.; Proud, C.; James, D.
31
vi Retinoic Acid Enhances Monoclonal Antibody Production of Human-Human Hybridoma BD9 Inoue, Y.; Fujisawa, M.; Shoji, M.; Hashizume, S.; Katakura, Y.; Shirahata
Extracellular Adenosine 5’ Monophosphate Controls Proliferation and Stimulates Protein Production of rCHO Cells Bonarius, H.P.J.; Hansen, K.; Kongerslev, L.
The Mode of Actions of Lysozyme as an Immunoglobulin Production Stimulating Factor (IPSF) Sugahara, T.; Murakami, F.; Sasaki, T.
35
39
43
A Dissection of Recombinant Protein Expression in CHO Cells Indicating Protein-Specific, not Cell Specific, Limitation Altobello, K.; Chung, YH.; Iovino, J.; Luchette, C.; Overton, S.; Cunningham, M. 47
Effect of Bioreactor Process Control Parameters on Apoptosis and Monoclonal Antibody Production During the Protein-Free Fed-Batch Culture of a Murine Myeloma Moran, E.; McGowan, St.; Reynolds, N.; Wilson, C.
51
Adenovirus Vector Production in 293 Fed-Batch Cultures Wong, K.; Guardia, M.J.; Lee, St.; Hu, W.-S. 55
Influence of BCL-2 Over-Expression on NS0 and CHO Culture Viability and Chimeric Antibody Productivity Tey, B.T.; Singh, R.P.; Al-Rubeai, M.
A Regulatable Selective System Facilitating Isolation of High Expression Mammalian Cells Teruya, K.; Zhang, Y.-P.; Katakura, Y.; Shirahata, S.
59
63
Comparative Analysis of IRES Efficiency of Dicistronic Expression Vectorsi n Primary Cells and Permanent Cell Lines Schumacher, L.; Alves, P.M.; Wirth, M. 67
Use of Gel Microdrops Selection System for Recombinant Cells
vii
Hansen, K.; Bertelsen, C.; Kongerslev, L. 71
Bovine Serum-Albumin with Grafted RGD Tailed Cyclic Peptides as an Engineered Proadhesive Protein Dewelle, J.; Delforge, D.; Pirotton, S.; Remacle, J.; Raes, M.
Matrix Attachment Regions in Stable CHO Cell Line Development Zahn, M.M.; Kobr, M.; Mermod, N.
75
79
High Cell Density Cultivation of Hybridoma Cells Spin Filter vs Immobilized Culture Heine, H.; Biselli, M.; Wandrey, C. 83
Influence of the Inoculum on the Production of Antibodies with Mammalian Cells Inglin, M.; Graf-Hausner, U.; Sonnleitner, B.; Spinnler, R.; Leist, Ch.
Establishing and Developing CHO Cell Lines for the Commercial Production of Human Anti-Rhesus D IgG De Jesus, M.; Bourgeois, M.; Jordan, M.; Zahn, M.; Mermod, N.; Amstutz, H.P.; Wurm, F.M.
Glucose and Glutamine Replacement for the Enhancement of Fed-batch Proceses Using CHO Cells Altamirano, C.; Paredes, C.; Cairo, J.J.; Godia, F.
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91
95
Pilot Scale Production of Human Prothrombin Using a Recombinant CHO Cell Line Lütkemeyer, D.; Heidemann, R.; Tebbe, H.; Gudermann, F.; Lehmann, J.; Schmidt, M.; Raditsch, M. 99
Maintenance of High Viability During Direct Transition of CHO-Kl Cell Growth from 10% to 0% Serum; No Adaptation Required Tsao, M.C.; Johnson, J.M.; Bachelder, C.; Wood, M.A.; Boline, J.A.; Berzofsky, R.N.
Analysis and Simultaneous Isolation of Recombinant t-PA Using High Performance Membrane Affinity Chromatography Renemann, G.; Kretzmer, G.; Tennikova, T.B.
103
107
viii CHAPTER II. Metabolic and Process Engineering
Improvement of the Primary Metabolism of Cell Cultures Introducing a Pyruvate Carboxylase Reaction Pathway Irani, N.; Wirth, M.; V.d. Heuvel, J.; Beccaria, A.J.; Wagner, R.
113
Growth Kinetic Studies (In Hours) Based on the Fluorescence of Stable, GFP-Expressing CHO Cells Hunt, L.; Jordan H.; De Jesus, M.; Wurth, F.; 119
Intracellular Localization of Non-Secreted Recombinant -Trace Protein in Vesicle-Like Structures of Baculovirus-Infected Insect Cells Schulze, N.; Albers, U.; Grabenhorts, E.; Conradt, H.S.; Rohde, M., Nimtz, M.; Jäger
Induction Kinetics of Apoptosis in Mammalian Cell Cultures Linz, M.; Zeng, A.-P.; Deckwer, W.-D.
123
127
A Model for the On-Line Scrutiny of Metabolism: Its Application to the Changing Nutritional Demands of Cultured Animal Cells Guan, Y.H.; Kemp, R.B. 131
Caspases as a Target for Apoptosis Inhibition in Hybridoma Cells in Culture Gabernet, C.; Tinto, A.; Vives, J.; Prats, E.; Cornudella, L.; Cairo, J.J.; Godia, F.
135
Cell Activity after Cell Growth Inhibition by the IRF-1 System Coroadinha, A.S.; Carvalhal, A.V.; Moreira, J.L.; Carrondo, M.J.T. 139
Establishment of a Primary Liver Cell Culture from a Teleost,Oreochromis Mossambicus, the Tilapia: a Valid Tool for Physiological Studies Schmid, A.C.; Kloas, W.; Reinecke, M.;
TGB Induces Premature and Replicative Senescence in Cancer Cells
143
Miura, T.; Katakura, Y.; Nakata, E.; Uehara, N.; Shirahata, S.
Development of a Fed-batch Strategy that Utilizes Multiple Carbon Sources to Maximize Recombinant Protein Expression in CHO Cells Deer, F., Cunningham, M.R.
Development of a New, Highly Flexible, Fully Computer Integrated Fermentor Control System Büntemeyer.; Nerkamp, M.; Bockholt, S.; Weber, C.; Gudermann, F.; Lehmann, J.
Cell Growth Rate Estimation in Packed-Bed and Hollow Fibers Bioreactors: Metabolism and Productivity Rodrigues, M.T.A.; Garbuio, A.; Nagao, L.T.; Raw, I.; Moro, A.M.
Influence of Oxygen Limitation on Myeloma Cell Cultures: Various Methods of Inoculum Proliferation for Bioreactor Cultivations Spinnler, R.; Graf-Hausner, U.; Inglin, M.; Leist, Ch.
Comparison of Fed-batch Strategies in Hybridoma Cultures Schwabe, J.O.; Wilkens, I.; Pöortner, R.
ix
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167
Non-Invasive Adaptive Control of the Feed Rate for High Cell Density CHO Cultures According to the On-line pO2 Profile Müller, D.; Doblhoff-Dier, O.; Katinger, H. 171
Cell Growth Control by the IRF-1 System in Perfusion Culture Carvalhal, A.V.; Moreira, J.L.; Carrondo, M.J.T.
Modulation of Cell Cycle for Optimal Recombinant Protein Production Hendrick, V.; Vandeputte, O.; Raschella, A.; Marique, T.; Cherlet, M.; Abdelkafi, C.; Wérenne, J.
Application of Bioassays for Suspended 293 Cell Enumerations in Chemically Defined Medium (CDM) Tsao, M.C.; Jacko, B.A.; Curnow, E.; Berzofsky, R.N.
175
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183
X
Efficient Cell Growth by an Optimised Protein Free Medium Design and a Controlled Feeding Strategy Loa, A.; Lefebvre, P.; Kretzmer, G.
Development of a Serum Free Medium for a Human Diploid Fibroblast Cell Line Pirotton, S.; Dewelle, J.; Eliaers, F.; Delforge, D.; Raes, M.
The Use of Peptones as Medium Additives for High-Density Perfusion Cultures of Animal Cells Heidemann, R.; Zhang, C.; Qi, H.; Rule, J.L.; Rozales, C.; Park, S.; Chuppa, S.; Ray, M.; Michaels, J.; Konstantinov, K.; Naveh, D..
Determination of Animal Cell Densities and Viability by the New Analyser CEDEX2 When, T.; Lorenz, Th.; Behrendt, U.; Wallerius, C.; Büntemeyer, H.; Lehmann, J.
Determination of Animal Cell Densities and Viability; Comparison of the Microcyte Flow Cytometer with Trypan Blue Counts and Coulter Count Vriezen, N.
Mid-Infrared Spectroscopic Monitoring of Animal Cell Culture Bioractor Processes Rhiel, M.; Ziegler, T.; Ducommun, P.; Von Stockar, U.; Marison, I.W.
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207
Mammalian Cell Monitoring using the Microcyte Flow Cytometer Harding, C.L.; Lloyd, D.r.; McFarlane, C.M.; Al-Rubeai, M. 211
Indirect Biomass Determination in Case of Non-Constant Metabolic Rates Ducommun, P., Ziegler, T.; Rhiel, M.; Von Stockar, U.; Marison, I.W. 215
Whole Cell – Smart Microsensor: A first Approach Towards Interfacing Live Cells and Electronics Charlier, O.; Goffaux, M.-J.; Marique, T.; Hendrick, V.; De Vos, L.; Werenne, J. 219
Comparison of Immobilised Group Specific Affinity Ligands for the Bioseparation of Antibodies by High Performance Membrane Affinity Chromatography Berruex, L.G.; Freitag, R.
CHAPTER III. Post-Translational Modifications
Posttranslational Modifications Limit High Level Expression of Functionally Active Chimeric P-Selectin Glycoprotein Ligand-1 in rCHO Cells Sinacore, M.S.; Richards, T.; Francullo, L.; Woodard, A.; Hardy, M.; Cornell, R.; Koza, S.; Davies, M.; Ellis, D.; Harrison, S.
Glycolsylation Analysis of Nanomolar Amounts of Glycoprotein Comtining In-gel Enzymatic Digestion and FACE™ Kloth, C.; Leibiger, H.; Valley, U.; Yalcin, E.; Buchholz, R.; Emmrich, F.; Marx, U.
xi
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229
237
Glycosylation Patterns of a rec-Fusion Protein Expressed in BHK Cells at Different Metabolic States Cruz, H.J.; Conradt, H.S.; Peixoto, C.M.; Alves, P.M.; Nimtz, M.; Dias, E.M.; Santos, H.; Moreira, J.L.; Carrondo, M.J.T. 241
Elimination of N-Glycolylneuraminic Acid Residues in Recombinant Glycoproteins: A Gene Knock-Out Approach Fontana, O.; Covini, N.; Pighini, M.; Carpani, D.; Buono, P.; Soria, M.R.; Monaco, L.
Fucosyltransferase III Production by Mammalian and Insect Cells for the Synthesis of Therapeutic Oligosaccharides Benslimane, C.; Chenu, S.; Tahrat, H.; Deparis, V.; Auge, C.; Cerutti, M.; Delannoy, P.; Goergen, J.L.; Marc, A.
245
251
Control of Therapeutic Monoclonal Antibody Glycosylation Hills, A.E.; Patel, A.K.; Boyd, P.N.; James, D.C. 255
The Effect of Cell Line, Transfection Procedure and Reactor Conditions on the Glycosylation of Recombinant Human
xii Anti-Rhesus D IgGl Nahrgang, S.; Kragten, E.; De Jesus, M.; Bourgeois, M.; Déjardin, S.; Von Stockar, U.; Marison, I.W.
259
Metabolic Engineering of Recombinant Plasminogen Sialylation in Animal Cells by Tetracycline-Regulated Expression of Murine CMP-NeuAc Synthetase and Hamster CMP-NeuAc Transporter Genes Baker, K.N.; Johnson, I.D.; Roberts, G.; Cook, A.; Baines, A.; Gerardy-Schahn, R.; James, D.C. 263
CHAPTER IV. Reactor Design and Operation
Air-Trap-Technology: Bubble-Free Gas Transfer in Large Scale Däscher, M.B.; Sonnleitner, B.; Georg, A.
269
The Improvement of Aeration in 8000 I Animal Cell Culture Vessels Clayton, T.M.; Jenkins, I.; Steward, P. 277
A Novel Continuous Suspension Culture System for Hematopoietic Cells Schmidt, S.; Jelinek, N.; Hilbert, U.; Thoma, S.; Wandrey, C.; Biselli, M.
285
Large Scale Production of HIV-I gp120 Using Recombinant Vaccinia Virus in Packed-Bed Bioreactor Kaufman, J.; Cho, M.W.; Lee, M.K.; Shiloach, J. 289
The “Shear Tester”. A Universal Tool for Characterization of the Shear Sensitivity of Animal Cell Lines under Various Process Conditions Flagmeyer, A.; Konstantinov, K.; Henzler, H.-J. 293
Membrane Oxygenation of Mammalian Cell Culture Fermenters Using DuPont Teflon AF-2400 Tubing Blackie, J.; Wu, P.; Naveh, D. 299
Configuration of a Simple Dialysis Membrane Bioreactor Suitable for Large-Scale Application Kleuser, B.; Kocher, H.P.; Memmert, K.; Stenz, M.;
Straubhaar, B.; Zurini, M.
xiii
303
Erythropoietin Production from CHO Cells Grown in a Fluidized-Bed Bioreactor with Macroporous Beads Wang, M.D.; Yang, M.; Huzel, N.; Butler, M. 307
Scale-Up of Fixed-Bed Reactors for the Cultivation of Animal Cells Fassnacht, D.; Reimann, I.; Pörtner, R.
311
A Novel Conical Shaped Bioreactor for Small-Scale Investigations under Defined Conditions Schwabe, J.O.; Matsuoka, H.; Jungkeit, H.; Pörtner, R. 315
Continuous Perfused Fluidized Bed Technology: Increased Productivities and Product Concentrations Müller, D.; Unterluggauer, F.; Kreismayr, G.; Schmatz, C.; Wiederkum, S.; Preis, S.; Vorauer-Uhl, K.; Assadian, A.; Doblhoff-Dier, O.; Katinger, H. 319
Small Scale Bioreactor System for Process Development and Optimization Girard, P.; Meissner, P.; Jordan, M.; Tsao, M.; Wurm, F. 323
CHAPTER V. Transient Gene Expression
Mammalian Transient Gene Expression-Potential, Practical Applications and Perspectives Blasey, H.D.; Hovius, R.; Rey, L.; Vogel, H.; Bernard, A.R. 331
Float! – And Express More: Converting the HEK.EBNA/oriP System to Suspension Culture Geisse, S.; Orakçi, O.; Pabler, A.; Patoux, A.; Rinaldi, D.; Watkins, J.; Schmitz, R.; Gram, H. 339
Multiplicity and Time of Infection as Tools to Maximize Virus-Like Particle Production by Insect Cells Palomares, L.A.; Lopez, S.; Arias, C.F.; Ramirez, O.T. 347
Process Development for Transient Gene Expression in Mammalian Cells at the 3 L Scale: 10-50 MG of R-Protein in Days
xiv
Meissner, P.; Girard, P.; Kulangara, A.; Tsao, M.C.; Jordan, M.; Wurm, F.M.
351
A Method to Determine the Optimal Time to Infect Insect Cells with the Baculovirus Expression System Ljunggren, J.; Alarcon, M.; Ramqvist, A.K.; Westlund, A.; Ohman, L. 359
Analysis of Baculovirus Infected Sf9 Cells Using Flow Cytometry Pettman, G.R. 363
Adaptation of Recombinant HEK-293 Cells to Growth in Serum-Free Suspension McAllister, R.C.; Schofield, C.; Pettman, G.R.; Mannix, C.
Growth on Microcarriers and Nutritional Needs of High Density Insect Cell Cultures Ikonomou, L.; Bastin, G.; Schneider, Y.-J.; Agathos, S.N.
367
371
UseCytometry in the Evaluation of Hydroxyapatiteof Flow for the Purification of DNA Plasmid Wright, J.L.; Egtard, P., Van Adrichen, J.; Freitag, R.; Wurm, F.M. 375
CHAPTER VI. Regulatory and Stability Issues in Animal Cell Culture for Pharmaceutical Production
Regulation and Standardisation of Gene Transfer Products in the European Union K. Cichutek 381
Study of Stability of Expression of a Humanized Monoclonal Antibody from a Transfected NSO Myeloma Cell Line Using Different Culture Media and Serum Concentrations Castillo, A.J.; Victores, S.; Marison, I.W.
Analysis of Alterations in Gene Expression after Amplification of Recombinant Genes in CHO Cells Hohenwarter, O.; Grillari, J.; Fortschegger, K.;
389