Animal Cell Technology: From Target to Market : Proceedings of the 17th ESACT Meeting Tylösand, Sweden, June 10-14, 2001

This book is the lasting product, a resource of up-to-date information in the scientific literature for the field of animal cell technology, as it was presented during a pleasant and stimulating meeting in Tylosand, Sweden, in June 2001. The title of the meeting, From Target to Market , indicates the usefulness of Animal Cell Technology during all steps in the pharmaceutical development process. Following the biotech products reaching the market, it shows an upward trend in the contribution of biotech products to total New Molecular Entity output in the nineties, which continued until 1996 when biotech represented 25% of the annual output. Since then the proportion has been decreasing. A perceived hurdle from a market perspective is that a protein per definition is biodegradable and thus requires intravenous, or for some drugs subcutaneous administration. New promising administration technologies such as pulmonary delivery were highlighted at this meeting. The emphasis on project selection prior to entry in the development phase has triggered a portfolio management using more extensive preclinical data before a development decision is taken. Animal cells have become a very important tool in the drug discovery process. The next generation of products will evolve from applications such as gene therapy, novel vaccines, cell therapy, and gene regulation. Animal cell technology has a major role to play in the post-sequence era. Front Matter....Pages i-lxxv Front Matter....Pages 1-1 In Vitro Testing of a New Substance with Anti-Tumor Activity on Mammalian Cells Using Flow Cytometry....Pages 3-5 Destabilization of Green Fluorescent Protein by Substitution of Its Amino-Terminal Residue....Pages 6-9 Anti-Tumor Activity of Noguchi Catalyser 21 TM , a Mineral Water Containing Natural Leaf Soil....Pages 10-12 Fermented Milk, Kefram-Kefir Enhances Glucose Uptake into Insulin-Responsive Muscle Cells....Pages 13-15 Optimization of Medium for M2 (Anti-Flag) Hybridoma Using Factorial Matrix Designs....Pages 16-19 Neurite Outgrowth Promoting Substance from a Marine Alga, Sargassum Macrocarpum ....Pages 20-22 Neutralization of the Biological Activity of Glycosylated and Non-Glycosylated hGM-CSF by Monoclonal Antibodies....Pages 23-25 High Cell Density Cultivation of Mast Cells in Fluidized-Bed and Fixed-Bed Bioreactors....Pages 26-28 Front Matter....Pages 29-29 Over-Expression of Protein Kinase Bα Enhances Recombinant Protein Expression in Transient Systems....Pages 31-36 100 Liter Transient Transfection....Pages 37-44 Application of Alphavirus Vectors in Drug Discovery....Pages 45-51 The Use of UCOE Vectors in Combination with a Preadapted Serum Free, Suspension Cell Line Allows for Rapid Production of Large Quantities of Protein....Pages 52-57 Overexpression of a Transcription Factor to Maximize Glycoprotein Production in an Inducible Expression System....Pages 58-65 Glucose Dehydrogenase as Detector Protein of Recombinant Fusion-Proteins Directly in SDS Gels....Pages 66-68 Successful Transfection of Partially Purified DNA in the HEK293EBNA Cell Line for Transient Expression....Pages 69-71 Capillary-Aided Cell Cloning....Pages 72-74 The Comparative Study of Cultural and Productive Characteristics of Different Recombinant Cell Lines Producing Human Erythropoietin....Pages 75-78 The Use of a C-FOS -GFP Reporter System for Monitoring Apoptosis of Animal Cells Induced by Exotoxins of Pseudomonas Aeruginosa ....Pages 79-82 High Performance Transient Expression in Mammalian Cells....Pages 83-87 In 30 Days from Plasmid to Product: Expression of a Secreted Fusion Protein Using Hek293-EBNA Cells....Pages 88-90 Front Matter....Pages 29-29 SF9 Cells Infection and Fuc-TIII Quality in Serum-Free and Serum-Containing Media....Pages 91-93 Rapid Expression of Recombinant Proteins in Modified CHO Cells Using the Baculovirus System....Pages 94-100 Recombinant Glycoprotein Production by CHO Cells in Low Protein Serum Free Medium....Pages 101-106 Arginine Is a Limiting Essential Amino Acid in Batch Cultures of Recombinant Chinese Hamster Orvary Cells Producing Thrombopoietin....Pages 107-109 Production of Recombinant Allergen Proder P 1 by CHO Cells Adapted to Grow in Serum-Free Suspension....Pages 110-113 Pilot Scale Production and Purification of a Soluble E-Selectin-IgG Chimeric Protein....Pages 114-117 Front Matter....Pages 119-119 Environmental Effects on Cell Physiology and Metabolism: Response to Elevated pC0 2 ....Pages 121-128 Improved Dual-Regulated Expression Systems for Independent Control of Two Different Transgenes....Pages 129-135 Metabolic Flux Analysis in Mammalian Cells — Network Modelling as an Example for Metabolic Design in Recombinant BHK Cells....Pages 136-142 Assessment of Keratin Expression and Xenobiotic Metabolism in Cultured Normal and Transformed Human Oral Keratinocytes....Pages 143-148 Regulation of Cell Cycle and Productivity in NS0 Cells by the Over-Expression of p21 CIP1 ....Pages 149-155 Loss of Productivity of a Transfectoma in Long-Term Culture: Recovery of Expression....Pages 156-159 Adaptation and Selection of NSO Myeloma Cell Lines Producing Recombinant Monoclonal Antibodies in Protein-Free Medium....Pages 160-163 Specific Effects of Synthetic Oligopeptides in Animal Cell Culture....Pages 164-167 Differential Enhancement of Monoclonal Antibody Production by Retinoids in Human Hybridomas....Pages 168-170 Regulation Mechanisms of Antibody Production from Human PBMC Immunized in vitro ....Pages 171-174 Influences of Glutamine Concentration on Cellular Metabolism in Continuous Culture of Hybridoma....Pages 175-178 Study of NS0 Cell Line Metabolism in Lipid Supplemented Protein Free Media....Pages 179-182 Metabolic Shifts in Hybridoma Cells Utilising Wheat Peptides....Pages 183-184 Bi-Phasic Culture Strategies Based on Medium Formulation: Substitution of Glucose by Galactose in CHO Culture....Pages 185-188 Front Matter....Pages 119-119 New Advanced Protein-Free, Animal Component-Free Medium for Recombinant Protein Expression in Adherent CHO Cell Cultures....Pages 189-192 Na + Is Responsible for Intra-Run Variations of Specific Productivity of CHO Cell Lines Producing Human Anti Rh D IgG in Bioreactors....Pages 193-196 The Influence of pH on Cell Growth and Specific Productivity of Two CHO Cell Lines Producing Human Anti Rh D IgG....Pages 197-199 The Modification of a Serum-Free Media Formulation for the Production of Reovirus and the Growth of Vero, MRC-5, MDCK and BHK Cell Lines....Pages 200-203 The Role of Vitamins in Cell Culture Media....Pages 204-206 Effect of Sodium Butyrate on Glycosylation of Recombinant Erythropoietin....Pages 207-209 Identification of Betacellulin as a Major Growth Factor in Foetal Bovine Serum and Development of a Recombinant Betacellulin Analogue for Use in Serum-Free Cell Culture....Pages 210-212 Monitoring Growth and Death of Vero Cells Cultivated in Bioreactor with Serum-Containing and Serum-Free Media....Pages 213-216 Effects of a Rice Protein Hydrolysate on Growth of CHO Cells and Production of Human Interferon-γ in a Serum-Free Medium....Pages 217-219 Suppressive Effect of Electrolyzed-Reduced Water on the Growth of Cancer Cells and Microorganisms....Pages 220-223 Transient Bcl- x L Overexpression Has Different Effects on Protein Production in Various CHO-Derived Cell Lines....Pages 224-226 Proteolytic Potential during Batch Cultivation in Serum Free Media of an IFN-γ Producing CHO Cell Line....Pages 227-229 Genetic Strategies for Apoptosis Protection of Hybridoma Cells Based on Overexpression of Cellular and Viral Proteins....Pages 230-233 Modulation of Cell Proliferation by Metabolic Engineering....Pages 234-237 S-Phase Synchronized CHO Cells Show Elevated Transfection Efficiency and Expression Using CA/PO 4 ....Pages 238-240 Expression of Yeast Pyruvate Carboxylate in hGM-CSF-Producing CHO Cells....Pages 241-243 The Influence of Culture Conditions on the Development of Trans-Epithelial Electrical Resistance (TEER) and the Junctional Complex of MDCK Cells....Pages 244-246 Bioreactor for Pharmaceutical Screening Generally Applicable for Primary Cells....Pages 247-249 Increasing Population of Amniotic Epithelial Cells....Pages 250-252 Evaluation of the Biological Activity of Some Hormones, Growth Factors and Drugs on Cultured Cells, Isolated from Animal and Human Reproductive Organs....Pages 253-257 Front Matter....Pages 119-119 Cultivation of Human Articular Chondrocytes for Autologous Transplantation....Pages 258-260 A Cell Culture System from the Eye Stalk of Penaeus Indicus ....Pages 261-265 Cytotoxicity of Pyrethroid Insecticides in Rat Hepatoma-Derived Fa32 Cells....Pages 266-268 New Technologies for Automated Cell Counting Based on Optical Image Analysis “The Cellscreen”....Pages 269-273 Application of an Acceleration-Stat to Study Insect Cell Metabolism....Pages 274-276 Front Matter....Pages 277-277 Factorial Design and Analysis for Rapid Development of an Antibody Production Process in CHO Cells....Pages 279-286 Development of a Large Scale Process for the Production of Recombinant Truncated Factor VIII in CHO Cells under Cell Growth Arrest Conditions....Pages 287-292 Continuous Perfusion versus Discontinuous Fed-Batch....Pages 293-300 The Use of Hydrocyclones for Mammalian Cell Retention in Perfusion Bioreactors....Pages 301-306 High Throughput Cultivation of Animal Cells Using Shaken Microplate Techniques....Pages 307-312 Continuous Isolation of rFVIII from Mammalian Cell Culture....Pages 313-317 Sodium Butyrate Treatment: A Study of Critical Parameters Using CHO Cell Lines Expressing the Green Fluorescent Protein....Pages 318-324 Development of a Robust Protocol for the Production of Recombinant Proteins up to 20-L Scale Using BEVS....Pages 325-327 Optimising the Production of a Nuclear Receptor in SF9 Cells Using Response Surface Analysis....Pages 328-331 Growth of High-Five TM Cells on Cultispher-S Microbarriers....Pages 332-334 Catching the Wave: The BEVS and the Biowave....Pages 335-337 Physiology of Insect Cells Cultured in a New Serum-Free Medium....Pages 338-340 Characterisation and Evaluation of a New Screening System for Animal Cell Culture....Pages 341-343 Development of Bioprocess Concepts on Vaccine Production: Influenza Virus as an Example....Pages 344-346 Assay of Serum and Animal Protein Free Media for the Production of a Veterinary Rabies Vaccine by BHK-21 Cells....Pages 347-350 Front Matter....Pages 277-277 Cell Cultivation System on the Basis of Porous Ceramic for the Production of Virus-Like Particles....Pages 351-353 Influence of Cell Culture Media on Adhesion of Animal Cells on Microcarriers....Pages 354-357 Comparison of Three Different Serum Free Media: Scale up of a Semi-Continuous CHO Cell Process in an Industrial Application....Pages 358-361 Use of Plant Peptone-Containing Serum-Free Media for the Cultivation of CHO Cells in Suspension and on Microcarriers....Pages 362-364 Application of Protein-Free Cell Culture Media for the Manufacturing of Biopharmaceuticals....Pages 365-368 Fluid Bed Granulation as an Alternative to Milled Powders to Improve Performance of Dry-Form, Serum-Free Nutrient Media....Pages 369-371 NanoColloids: A New Method for Solubilization of Lipophilic Substances Used in Cell Culture....Pages 372-374 Development and Validation of a Novel Process for the Production of Powdered Cell Culture Media....Pages 375-378 Separation of Mammalian Cells Using a Specially Designed Rotating Disc Filter....Pages 379-381 Comparison of Fluidised Bed and Ultrasonic Cell-Retention Systems for High Cell Density Mammalian Cell Culture....Pages 382-385 Ultrasonic Cell Separation — Production of Monoclonal Antibodies in Continuous Perfusion Cultures....Pages 386-388 Increased Production Yields of Native Interferon-γ in Membrane Bioreactors by Continuous Harvest....Pages 389-392 Production of rhEPO in Hollow Fibers’ Bioreactor....Pages 393-395 Production of rhEPO under Variants of Cultivation Media....Pages 396-398 Solution to the high Dissolved CO 2 Problem in High-Density Perfusion Culture of Mammalian Cells....Pages 399-402 Perfusion Cell Culture in Disposable Bioreactors....Pages 403-409 Process Development in a Packed Bed Bioreactor....Pages 410-411 The Art & Science of Micro-Sparging in High-Density Perfusion Cultures of Animal Cells....Pages 412-415 Culture of the CB.Hep-1 Hybridoma Using Different in vitro Systems....Pages 416-418 Selection of Suitable Anti-rHBsAg Mabs for in vitro Production....Pages 419-421 Front Matter....Pages 277-277 Reorganizing of Monoclonal Antibodies Process in the Era of Human Genome Cloning....Pages 422-426 Production of a Highly Pure Mab from Cell-Pharm System CP-2500....Pages 427-430 How Does Protein Free Medium TurbodomaTM HP-I Perform in Mouse Hybridoma Cultures in Different Culture Systems?....Pages 431-433 Effect of Seed Cell Density on Specific Growth Rate Using CHO Cells as Model....Pages 434-437 Adaptation and Growth Kinetics of the Universal Host CHO Cell Lines in Serum-Free Medium....Pages 438-440 Process Development for Functional Membrane Receptor Production in Mammalian Cells....Pages 441-445 Development of an Automated, Adaptive Model-Based Control for the Effective Cultivation of Hybridoma Cells....Pages 446-448 The One Step Inoculation Concept: A New Seed-Train Expansion for Recombinant Mammalian Cell Lines....Pages 449-451 In-Situ Microscopy for On-Line and In-Line Monitoring of Cell Populations in Bioreactors....Pages 452-454 Measurement of the Viable Cell Density: Validation and Integration of On-Line and Off-Line Capacitance Biomass Monitors for Cell Culture Processes....Pages 455-458 Robot Automation of Sampling and Sample Management during Cultivation of Mammalian Cells in Pilot Scale....Pages 459-462 Rapid Estimation of Human Monoclonal Antibody (IgG4) Concentration in Cell Culture Supernatants....Pages 463-465 Use of Ion-Exchange Membrane Adsorbers for Production of Biopharmaceuticals....Pages 466-468 Front Matter....Pages 469-469 Pharmaceuticals Produced by Biotechnology: Quality and Safety Issues....Pages 471-476 Factory IQ/OQ, A New Approach for Streamlining Validation of Cell Culture Equipment....Pages 477-481 Critical Issues for the Use of Tangential Flow Filtration Systems for Cell Harvesting Applications....Pages 482-484 A General Method for the On-Line RT-PCR Detection of Retrovirus Contamination in Cell Lines Used for Protein and Viral Vector Production....Pages 485-487 Novel Assay for Protein Impurities in Biopharmaceuticals Based on Fluorescence Intensity Distribution Analysis (FIDA)....Pages 488-490 Development of Mammalian Cell Bioreactor Processes....Pages 491-493 Front Matter....Pages 495-495 Development of Microgranulated Form of the Live Measles Vaccine....Pages 497-499 Front Matter....Pages 501-501 Bioprocess Development for the Cultivation of Human T-Lymphocytes....Pages 503-509 Adenovirally Modified Dendritic Cells for Immunotherapy: From Basic Development to Clinical Application....Pages 510-516 GMP Compliant Expansion of Hematopoietic Stem Cells (CD34+) Selected from Cord Blood for a Phase I Cell Therapy Trial....Pages 517-522 Multi-Plasmid Vaccines for HIV-1: Issues and Advancements....Pages 523-531 Continuous Retroviral Vector Production in a Perfusion Bioreactor System....Pages 532-534 Monolayer and Suspension Cultures of HEK 293 Cells for Recombinant Adenovirus Production for Gene Therapy: Effect of “Cell Passage Number”....Pages 535-537 Possible Strategies for the Production of Viral Vector: The Role of Engineering Design....Pages 538-540 Establishing Novel Hepatoma Cell Line for Bioartificial Liver....Pages 541-544 An Improved Oxygenation Hollow Fiber Bioreactor for the Cultivation of Liver Cells....Pages 545-547 Medium for Gene Therapy: Improved Protein-Free Media for Growth and Production of Viral Vectors for Use in Gene Therapy....Pages 548-552 Induction of a T Helper Cell Response against the Tumor Associated Antigen Her-2 Using Monocyte-Derived Dendritic Cells....Pages 553-557 Cultivation of Human HCMV Specific Lymphocytes — An Example for Adoptive Immunotherapy....Pages 558-561 Application of hTERT Promoter to Cancer Therapy....Pages 562-564 Establishment of a Genetic System to Coordinate Feeder Cell Growth in Cocultures with Primary Cells....Pages 565-567 Construction and Operation of a Bioreactor for Three-Dimensional Cartilage-Implants....Pages 568-570 Tissue Engineering of Meniscal Cartilage....Pages 571-573 Anti-Oxidative Water Improves Diabetes....Pages 574-577 Effect of Transfection-Induced Changes in Expression of Insulin-Like Growth Factor Binding Proteins on Secretory Activity and Responses of Ovarian Cell Cultures....Pages 578-580 Cultivation of Primary Osteogenic Cells in Serum-Reduced or Serum-Free Culture Media: Attachment, Proliferation and Differentiation....Pages 581-583 Back Matter....Pages 585-595 This book is the lasting product, a resource of up-to-date information in the scientific literature for the field of animal cell technology, as it was presented during a pleasant and stimulating meeting in Tylösand, Sweden, in June 2001. The title of the meeting, From Target to Market, indicates the usefulness of Animal Cell Technology during all steps in the pharmaceutical development process. Following the biotech products reaching the market, it shows an upward trend in the contribution of biotech products to total New Molecular Entity output in the nineties, which continued until 1996 when biotech represented 25% of the annual output. Since then the proportion has been decreasing. A perceived hurdle from a market perspective is that a protein per definition is biodegradable and thus requires intravenous, or for some drugs subcutaneous administration. New promising administration technologies such as pulmonary delivery were highlighted at this meeting. The emphasis on project selection prior to entry in the development phase has triggered a portfolio management using more extensive preclinical data before a development decision is taken. Animal cells have become a very important tool in the drug discovery process. The next generation of products will evolve from applications such as gene therapy, novel vaccines, cell therapy, and gene regulation. Animal cell technology has a major role to play in the post-sequence era This book is the lasting product, a resource of up-to-date information in the scientific literature for the field of animal cell technology, as it was presented during a pleasant and stimulating meeting in Tylosand, Sweden, in June 2001. The title of the meeting, __Target to Market__ A perceived hurdle from a market perspective is that a protein per definition is biodegradable and thus requires intravenous, or for some drugs subcutaneous administration. New promising administration technologies such as pulmonary delivery were highlighted at this meeting. The emphasis on project selection prior to entry in the development phase has triggered a portfolio management using more extensive preclinical data before a development decision is taken. Animal cells have become a very important tool in the drug discovery process. The next generation of products will evolve from applications such as gene therapy, novel vaccines, cell therapy, and gene regulation. Animal cell technology has a major role to play in the post-sequence era. Proceedings of the 17th ESACT Meeting June 10-14, 2001, Tylösand, Sweden