Production of Biologicals from Animal Cells in Culture

Production of Biologicals from Animal Cells in Culture

1st Edition - January 1, 1991

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  • Editors: R. E. Spier, J. B. Griffiths, B. Meignier
  • eBook ISBN: 9781483165158

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Production of Biologicals from Animal Cells in Culture reviews the state of the art in animal cell biotechnology, with emphasis on the sequence of events that occur when generating a biological from animal cells in culture. Methods that enable adjustment of nutrient feed streams into perfusion bioreactors so as to increase productivity are described. A number of issues are also addressed, such as the usefulness of the fingerprint method for cell characterization. Comprised of 135 chapters, this book begins with an overview of the problems and benefits of animal cell culture, followed by a discussion on the isolation of immortal murine macrophage cell lines. The reader is systematically introduced to the use of DNA fingerprinting to characterize cell banks; immortalization of cells with oncogenes; lipid metabolism of animal cells in culture; and energetics of glutaminolysis. Subsequent chapters explore serum-free and protein-free media; the physiology of animal cells; gene expression in animal cell systems; and animal cell bioreactors. The monitoring and assay of animal cell parameters are also considered, along with downstream processing and regulatory issues. This monograph will be of interest to students, practitioners, and investigators in the fields of microbiology and biotechnology.

Table of Contents

  • Hyclone Award Lecture

    1. Animal Cell Culture: The Problems and Rewards

    Section 1 Cell Lines and their Characterization

    2. The Isolation of Immortal Murine Macrophage Cell Lines

    3. Propagation of Human CD4-Immunoglobulin Producing Cell Lines

    4. Characterization of Cell Banks by DNA Fingerprinting

    5. Evaluating the Safety of Murine and Human Hybridomas: New Problems and New Techniques

    6. Defective Endogenous Retroviruslike Particles of Chinese Hamster Ovary Cells

    7. Reference Cell Lines

    8. A European Database for Animal Cell Lines

    9. Cell Line Data Base: an On-Line Data Bank Where Industry Meets Researchers

    10. Adhesion and Motility of Embryonic and Cancer Cells

    11. Immortalization of Cells with Oncogenes

    Section 2 Nutrient Media with Special Supplements

    12. Lipid Metabolism of Animal Cells in Culture - A Review

    13. Lipoprotein Requirements of Cultured Mammalian Cells

    14. Effect of Nutrients and Waste Metabolites on Growth, Metabolism and Protein Synthesis in Hybridoma

    15. Hybridoma Growth, Metabolism, and Product Formation in Hepes-Buffered Medium: Effect of Passage Number and pH

    16. A Screening Experiment of Media Supplements on CHO Cells

    17. Energetics of Glutaminolysis - A Theoretical Evaluation

    18. Degrading Effect of Light on Cell Culture Media

    19. Culture of Hybridoma in Dialysed Media

    20. Evaluation of Fetal Bovine Serum Substitutes on Cell Growth and Recombinant Protein Production

    21. Cell Growth Activators (CGA) and Cell Function Modulators (CFM) of Blood: Effect on Cell Replication and Protein Expression

    22. Increased Expression of Factor VIII by Butyrate in Chinese Hamster Ovary Cells

    23. Polyamine Enhanced Product Expression from Transformed and Recombinant Cell Lines

    24. The Development of a Process for the Production of HIV1 GP120 from Recombinant Cell Lines

    25. 'Safe' Animal Derived Medium Supplements for Cell Cultures

    26. Effect of Desferrioxamine on Transferrin Receptor Expression, Growth and IgG Production of the Rat Hybridoma MA C57

    Section 3 Serum-Free and Protein-Free Media

    27. Development of Serum-Free Media for Mammalian Cell Culture

    28. Concept and Strategy for the Development of a General Purpose Serum-Free Medium for Anchorage-Dependent Cells

    29. Growth of Mammalian Cell Lines Under Serum-Free Conditions

    30. Development of a Low-Serum Growth Medium for Production of a Human Glycoprotein by Recombinant BHK Cells

    31. Optimalisation of a Serum Free Medium for Large Scale Continuous Growth and Immunoglobulin Production by a Mouse Hybridoma

    32. Longterm Serum-Free Culture of Murine Hybridomas

    33. Serum-Free Media Suitable for Upstream and Downstream Processing

    34. Production of Human Fibronectin from Serum-Free Continuous Cultured Human Hepatoblastoma Line HUH-6

    35. Development of a Protein-Free Medium for Bioreactor Cultures of Hybridoma Cell Lines

    36. Conditions for the Production of Recombinant IL-2 in Stirred Suspension Culture Using a Protein-Free Medium

    37. A Protein-Free Serum Replacement (SSR) for Cell Culture

    38. Adaptation and Characterization of Hybridomas Growing in Low Protein and Protein-Free Medium

    39. Characterization of Protease Activity in Serum-Free Culture Supernatants of Hybridomas and Recombinant Mammalian Cells

    Section 4 Cell Physiology

    40. Animal Cells in Culture Make Secondary Metabolites too

    41. Removal of Inhibitory Factors from Hybridoma Cell Cultures by Gel Filtration

    42. The Effect of Metabolic by-Products on Animal Cells in Culture

    43. Cytoskeletal Microfilament Network and Energy Metabolism Affect Ability of Animal Cells to Resist Shear Injury

    44. Intracellular Concentration of ATP and other Nucleotides During Continuous Cultivation of Hybridoma Cells

    45. Determination of the 'Critical Shear Stress Level' for Adherent BHK Cells

    46. Effects of Dissolved Oxygen Supply and Glucose Concentration on Human Lymphoblastoid Cell Growth and Metabolism in Continuous Culture

    47. The Role of Dissolved Oxygen in Growth of Animal Cells

    48. The Effect of Osmolarity on Hybridoma Cell Growth and Antibody Production in Serum-Free Growth Media

    49. Physiological Investigations in High Density Perfusion Culture of Free Suspended Animal Cells

    50. Factors Affecting Hybridoma Cell Attachment to Derivatized Polyacrylamide Beads

    51. Adaption of Anchorage-Dependent Cells to Glutamine-Free Medium

    52. The 2'5' Oligoadenylate Synthetase, a Multienzyme System Involved in the Growth Properties and the Sensitivity to Viruses of Mammalian Cells: Selection of Antibodies in Order to Investigate their Specific Biological Roles

    Section 5 Gene Expression in Animal Cell Systems

    53. Recent Developments in Mammalian Expression Systems

    54. Genetic Engineering of Cellular Physiology

    55. Stability of Amplified DNA in Chinese Hamster Ovary Cells

    56. Methotrexate and CHO Cells: Productivity and Genetics of Amplified Expression Vector Sequences

    57. The Stability of Expression of Hybridoma Cells in Homogeneous Continuous Culture Systems

    58. Cloning and Expression of a Bovine Anti-Testosterone Monoclonal Antibody

    59. Use of Dicistronic Transcription Units for the Correlated Expression of Two Genes in Mammalian Cells

    60. Large-Scale Recombinant Protein Production Using the Insect Cell-Baculovirus Expression System: Antistatin and β-Adrenergic Receptor

    61. Quantitation of mRNA Specific for Heavy and Light Chains of IgG in Hybridomas During Different Phases of Batch Culture

    Section 6.1 Bioreactors: Overview

    62. Development of Mammalian Cell Manufacturing Processes

    63. A New Look at Animal Cell Bioreactor Development

    64. Mammalian Cell Fermentation: Are Specialized Bioreactors a Necessity?

    Section 6.2 Bioreactors: Hardware

    65. Engineering for Sterility and Containment: Design of a 225 L 'Polymodal' Fermenter for the Containment of P3 Pathogens

    66. Monoclonal Antibody Production Using an Airlift Fermentation System Consisting of a Continuous Seed Fermenter and a Fed Batch Production Fermenter

    67. Bleeding Out Dead Cells from Fermentation Systems

    68. High Intensity Growth of Adherent Cells on a Porous Ceramic Matrix

    69. Considerations in the Design, Development and Scale-Up of Glass Bead Packed Reactors

    70. On-Line Removal of Cells from Continuous Suspension Cultures

    Section 6.3 Bioreactors: Particles

    71. Microsphere-Induced Aggregate Culture of Animal Cells

    72. The Growth of CHO and BHK Cells as Suspended Aggregates in Serum-Free Medium

    73. CultiSpher - Macroporous Gelatin Microcarrier - New Applications

    74. Cultivation of CHO cells on Microcarriers Dormaceli

    Section 6.4 Bioreactors: Membranes and Perfusion

    75. Fermentation of AT III Producing BHK Cells in a Double Membrane Perfusion Bioreactor

    76. Oxygen Transfer Characteristics in Cell Culture Fermenters: Direct Sparging-Membrane Oxygenation-Bubble-Free Aeration Through a Rotating Sieve

    77. Hybridoma Culture in a Membrane System: The Influence of Oxygen on a Reactor's Performance and on the Evaluation of Cellular Density

    78. Hybridoma, Antibody and Growth Factor Distributions in the Shell-Side of Ultrafiltration Hollow Fiber Bioreactors

    79. Cultivation of Insect Cell Lines in Stirred Membrane Reactors

    80. High Density Culture of Hybridoma Cells Using a Perfusion Culture Apparatus with Multi-Settling Zones

    81. High Cell Density Perfusion Culutre of Insect Cells for Production of Baculovirus and Recombinant Protein

    Section 6.5 Bioreactors: Optimization via Metabolism

    82. Metabolite Parameters Modulating Monoclonal Antibody Production by Hybridoma Cells in Flask and Macroporous Glass Sphere Culture

    83. Optimization of OKT3 Hybridoma Cultures in a Perfusion Stirred Reactor

    84. Biochemical Control of Monoclonal Antibody Secretion in Hollow Fibre Reactors

    85. Optimization of Human Anti-Rhesus IgG Production Using Hollow Fiber Technology

    86. Parameters for Optimization of Fermentation of an AT III Producing Cell Line

    87. Enhanced Productivity of Hybridoma and Recombinant CHO Cell Cultures by Pluronic F-68 and other Medium Components, and by Increased Perfusion Rates, in Fluidized-Bed Bioreactors

    88. Improved Performance of the Fluidized Bed Reactor for the Cultivation of Animal Cells

    Section 6.6 Bioreactors: Comparative Studies

    89. Bioreactors for Production of HIV - A Comparative Evaluation of Flask, Suspension and Fixed Bed Cultures

    90. Comparison of Semicontinuous Culture and Perfusion Culture in a 75 L Bioreactor

    91. Comparison of Two Systems Based on Porous Beads for the Production of Recombinant von Willebrand Factor by CHO Cells

    92. Comparison of the Production Efficiency of Mammalian Cells Grown in a Fluidized Bed and in a Stirred Tank Reactor

    93. Monoclonal Antibody Production of Three Different Hollow Fibre Bioreactor Configurations

    94. A Comparison of Two Reactors for Cell Cultivation

    Section 7 Monitoring and Assay of Animal Cell Parameters

    95. Staining of Chinese Hamster Ovary Cells on Macroporous Matrices

    96. The Role of Oxidation-Reduction Potential in Monitoring Growth of Cultured Mammalian Cells

    97. Potential and Pitfalls of Using LDH Release for the Evaluation of Animal Cell Death Kinetics

    98. Flow Cytometric (FCM) Analysis on the Genetic Stability of Continuous Cell Lines

    99. Biomass Estimation in Anchorage-Dependent Animal Cell Cultures

    100. Dynamic Assay of Synthetic Activities in Single Hybridoma Cells

    101. Rapid Monitoring of Monoclonal Antibodies in Cell Culture Media by High Performance Liquid Affinity Chromatography (HPLAC)

    102. Application of the PCFIA to Rapid Off-Line Process Monitoring

    Section 8 Kinetics and Modeling

    103. Mathematical Estimator for the Evaluation of Cell Density and Medium Composition in Hybridoma Cultures

    104. Kinetic Effect of Growth Factors on Batch and Continuous Hybridoma Cultures

    105. Batch Production Kinetics of Hybridomas: Pulse Experiments

    106. Analysis of Hybridoma Growth, Metabolism and Product Formation in Continuous Suspension Culture

    107. Kinetics of Nutrient Utilization in a Hybridoma Batch Culture

    108. Modeling Growth of and Antibody Production by Hybridomas in Glutamine Limited Suspension Cultures

    109. A Computer Simulation of the Kinetics and Energetics of Hybridoma Cell Growth and Antibody Production

    110. A Kinetic Model for the Influence of Serum in Batch and Continuous Hybridoma Cultures

    Section 9 Downstream Processing

    111. Isolation of Biologicals: Leachables and Cleaning in Place Become a Crucial Issue in Liquid Chromatography

    112. Composite High Flow Rate Ion Exchangers for Economical Scale-Up

    113. Serum Free Media (SFM) and Serum Substitutes (SS) in Animal Cell Culture: Downstream Considerations

    114. The Use of Affinity Chromatography for the Purification of Monoclonal Antibodies

    Section 10 Products

    115. Production of a Pharmaceutical Enzyme: Animal Cells or E. coli?

    116. Oral Polio Vaccine (Sabin) Produced on Large-Scale Vero Cell Culture

    117. Strategies for Improved Production of Epstein-Barr Virus

    118. Optimal Conditions for the Growth of Pig Kidney Endothelial Cells (SK) Proliferated on Microcarriers and Production of Pig Parvovirus (PPV) Vaccine

    119. Continuous Production of a Novel Thrombolytic from 50/100 Litre Perfused Microcarrier Cultures

    120. Production of Recombinant Human Thyrotropin and its Incomplete Processing

    121. Production of a Monoclonal Antibody Against Gelsolin

    122. Appearance of Nonspecific Amounts of Monoclonal Antibody During Fermentation Caused by Decreased Cell Viability

    123. Production of Biologically Active Insulin-Like Growth Factor by Cells Transfected with a Recombinant Retroviral Vector Encoding IGF-1 726

    124. In vitro Production of Growth Regulators for Human Epithelial Cells

    125. Purification and Characterization of Immunoglobulin Production Stimulating Factor II? Derived from Namalwa Cells

    126. Production of a Chimeric Antibody from Tumor Imaging and Therapy from Chinese Hamster Ovary (CHO) and Myeloma Cells

    127. Optimization of tPA Production in a 3L Continuous Perfusion Bioreactor

    128. The Production and Assay of tPA from Mammalian Cells

    129. Constitutive Secretion of Soluble CD23 Receptors in Hollow Fiber Reactors

    130. Production of Proteins from Cell Nuclei by Cyclic Continuous Fermentation

    Section 11 Regulatory Issues

    131. Biologicals and Regulatory Aspects in the EEC

    132. Mapping of N-Linked Oligosaccharides from Human Recombinant Glycopro Teins: Quality Control of Glycosylated Therapeutic Polypeptides

    133. Validation of Downstream Processing

    134. The Culture Environment Affects Recombinant Protein Processing in CHO Cells

    135. The Medi-Cult Hybritest - A New Test for in Vitro Toxicology

    List of Exhibitors

    List of Participants

    Subject Index

    Author Index

Product details

  • No. of pages: 852
  • Language: English
  • Copyright: © Butterworth-Heinemann 1991
  • Published: January 1, 1991
  • Imprint: Butterworth-Heinemann
  • eBook ISBN: 9781483165158

About the Editors

R. E. Spier

J. B. Griffiths

B. Meignier

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