Production of Biologicals from Animal Cells in Culture
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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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