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Therapeutic Antibody Engineering
Current and Future Advances Driving the Strongest Growth Area in the Pharmaceutical Industry
- 1st Edition - October 16, 2012
- Authors: William R Strohl, Lila M Strohl
- Language: English
- Paperback ISBN:9 7 8 - 0 - 0 8 - 1 0 1 4 2 7 - 1
- Hardback ISBN:9 7 8 - 1 - 9 0 7 5 6 8 - 3 7 - 4
- eBook ISBN:9 7 8 - 1 - 9 0 8 8 1 8 - 0 9 - 6
The field of antibody engineering has become a vital and integral part of making new, improved next generation therapeutic monoclonal antibodies, of which there are currently more… Read more
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Request a sales quoteThe field of antibody engineering has become a vital and integral part of making new, improved next generation therapeutic monoclonal antibodies, of which there are currently more than 300 in clinical trials across several therapeutic areas. Therapeutic antibody engineering examines all aspects of engineering monoclonal antibodies and analyses the effect that various genetic engineering approaches will have on future candidates. Chapters in the first part of the book provide an introduction to monoclonal antibodies, their discovery and development and the fundamental technologies used in their production. Following chapters cover a number of specific issues relating to different aspects of antibody engineering, including variable chain engineering, targets and mechanisms of action, classes of antibody and the use of antibody fragments, among many other topics. The last part of the book examines development issues, the interaction of human IgGs with non-human systems, and cell line development, before a conclusion looking at future issues affecting the field of therapeutic antibody engineering.
- Goes beyond the standard engineering issues covered by most books and delves into structure-function relationships
- Integration of knowledge across all areas of antibody engineering, development, and marketing
- Discusses how current and future genetic engineering of cell lines will pave the way for much higher productivity
Microbiologists, biochemists, oncologists;
List of figures
List of tables
List of acronyms, abbreviations, and definitions
Foreword
Preface
About the authors
Chapter 1: Introduction to biologics and monoclonal antibodies
Abstract:
1.1 Introduction
1.2 Definitions of biologies
1.3 Recombinant protein therapeutics
1.4 MAbs and Fc fusion proteins (FcFPs)
1.5 General anatomy of a therapeutic IgG MAb
1.6 Naming convention for antibodies from different sources
Chapter 2: Value proposition for therapeutic monoclonal antibodies and Fc fusion proteins
Abstract:
2.1 Overview of discovery and development of therapeutic MAbs and FcFPs
2.2 Market for MAbs and FcFPs
2.3 Currently and recently approved MAbs and FcFPs
Chapter 3: Antibody structure–function relationships
Abstract:
3.1 Introduction
3.2 Constant region structure/function
3.3 FAb structure/function
Chapter 4: Fundamental technologies for antibody engineering
Abstract:
4.1 Introduction
4.2 Hybridoma technology – the gateway for therapeutic monoclonal antibodies
4.3 Key recombinant DNA technologies
4.4 Generation of chimeric antibodies
4.5 Display technologies
4.6 Maturity timelines for biologies technologies
Chapter 5: Sources of antibody variable chains
Abstract:
5.1 Human antibody gene organization
5.2 Antibody gene rearrangement and diversity in vivo
5.3 Sources of antibody diversity
5.4 Class-switch recombination
5.5 Human variable gene usage
5.6 Variable region selection
5.7 Variable genes from non-human species
5.8 Use of variable genes from humans
Chapter 6: Variable chain engineering – humanization and optimization approaches
Abstract:
6.1 Introduction
6.2 Chimerization
6.3 Humanization
6.4 Affinity optimization
Chapter 7: Antibody interactions with the immune system
Abstract:
7.1 Introduction
7.2 Human Fcγ receptors
7.3 FcRn and its effect on MAb and FcFP half-life
7.4 Other Fc receptors of importance
7.5 Complement activation
Chapter 8: Monoclonal antibody targets and mechanisms of action
Abstract:
8.1 Properties of antibody targets
8.2 Antibody mechanisms of action
8.3 CD20 – example of a target for which multiple MOAs apply
Chapter 9: Therapeutic antibody classes
Abstract:
9.1 Human antibody overview
9.2 Human IgG isotypes
9.3 IgM
9.4 IgA
Chapter 10: Antibody Fc engineering for optimal antibody performance
Abstract:
10.1 Antibody engineering for decreased or increased effector function
10.2 Current marketed MAbs and clinical candidates with modified Fc
10.3 The effect of human Fc polymorphisms on disease and therapeutic index
10.4 Fc engineering of IgGs to increase effector function
10.5 Fc engineering for silenced effector function
10.6 FcγRIIb-dependent suppression of immune response
10.7 Antibody engineering for modulation of pharmacokinetics
10.8 Tissue targeting
Chapter 11: IgG glycans and glyco-engineering
Abstract:
11.1 Introduction to Fc glycosylation
11.2 Non-glycosylated IgGs for lowered effector function
11.3 Low- or non-fucosylated oligosaccharides result in higher ADCC
11.4 Non-sialylated IgG glycans result in increased ADCC
11.5 Sialylated IgG glycans may result in immunosuppressive effects
11.6 High-mannose glycoforms
11.7 FAb glycosylation
Chapter 12: Antibody fragments as therapeutics
Abstract:
12.1 Introduction to antibody fragments and alternative formats
12.2 FAb and scFv antibody fragments
12.3 Domain antibodies, including nanobodies, IgNARs, and nanoantibodies
12.4 Antibody size and tissue distribution
12.5 Strategies for half-life extension of antibody fragments
12.5.2 PEGylation
Chapter 13: Multiple antibody and multi-specificity approaches
Abstract:
13.1 Introduction
13.2 Serum therapy
13.3 IVIG
13.4 Multi-antibody approaches
13.5 Bispecific antibodies based on IgGs
13.6 Bispecific antibody fragments
Chapter 14: FcFPs and similar constructs using Fc
Abstract:
14.1 Introduction
14.2 Receptor-FcFPs
14.3 Traps: multi-ligand binding domains of different receptor chains fused to Fc region
14.4 Soluble protein FcFPs
14.5 Antibody fragment – Fc fusion proteins
14.6 Fc peptide fusions as receptor agonist therapeutics
14.7 Other FcFP structures
14.8 Issues to consider with FcFPs
Chapter 15: Antibody-drug conjugates
Abstract:
15.1 Introduction to antibody-drug conjugates
15.2 Overview and anatomy of a typical ADC
15.3 ADC antibodies and targets
15.4 ADC chemical “warheads”
15.5 ADC linkers
15.6 Issues, limitations, and design of ADCs
15.7 Radioimmunoconjugates
15.8 Protein immunotoxins
15.9 ADEPT
15.10 Other ADC-like approaches
Chapter 16: Development issues: antibody stability, developability, immunogenicity, and comparability
Abstract:
16.1 Introduction
16.2 Aggregation
16.3 Lack of desired solubility
16.4 Fragmentation
16.5 Post-translational amino acid residue modifications
16.6 Instability and isomerization of disulfide bonds
16.7 Stability at low pH
16.8 Glycosylation issues
16.9 Immunogenicity
16.10 Biocomparability
Chapter 17: Interactions of human IgGs with non-human systems
Abstract:
17.1 Introduction
17.2 Non-human primate IgGs and Fcγ receptors
17.3 Mouse IgGs and Fcγ receptors
Chapter 18: Cell line development
Abstract:
18.1 Introduction
18.2 Process summary
18.3 Key issues in cell line development
18.4 Choice of cell line
18.5 Mammalian cell lines
18.6 Microbial cells
18.7 Multiple cell lines in single batches
18.8 Gene and vector optimization and selectable markers
18.9 Other industry trends
Chapter 19: Issues facing therapeutic monoclonal antibodiesfor the future
Abstract:
19.1 Introduction to the future state
19.2 Commoditization of the core underlying technologies
19.3 Impact of follow-on MAbs and FcFPs
19.4 Competition
19.5 The continued need for, and limitation of, novel pre-clinically validated targets
19.6 Payor pressure
19.7 Pipeline in a product concept
19.8 Companion diagnostics and patient segmentation
19.9 Treatment with multiple antibodies and bispecific antibodies
19.10 MAb and FcFP conjugates
19.11 Biopharma in 2020 – the focus on BRIC
19.12 SWOT analysis of therapeutic MAbs and FcFPs
19.13 Epilogue
Useful public websites related to antibody engineering
References
Index
- No. of pages: 696
- Language: English
- Edition: 1
- Published: October 16, 2012
- Imprint: Woodhead Publishing
- Paperback ISBN: 9780081014271
- Hardback ISBN: 9781907568374
- eBook ISBN: 9781908818096
WS
William R Strohl
Dr William R. Strohl is Vice President of Biologics Research at Janssen R&D Biotechnology Center of Excellence, and was previously a leader in Merck’s efforts to discover therapeutic monoclonal antibodies, as well as in-licensing of therapeutic targets and technologies associated with monoclonal antibodies. He has over 100 publications and several patents to his credit, and has edited two books.
Affiliations and expertise
Johnson & Johnson Biotechnology Center of ExcellenceLS
Lila M Strohl
Affiliations and expertise
Medical Illustrator, USARead Therapeutic Antibody Engineering on ScienceDirect