This item is in: Biomedicine > Pharmaceutical science/technology, drug delivery
Therapeutic antibody engineering: Current and future advances driving the strongest growth area in the pharmaceutical industryW R Strohl, Johnson & Johnson Biotechnology Center of Excellence and L M Strohl, Medical Illustrator, USA
Woodhead Publishing Series in Biomedicine No. 11
An excellent balance between readability and depth of material.... The book is well referenced and provides plentiful opportunities to continue subject-specific learing.
mAbs Journal
An excellent book describing many aspects of therapeutic antibody generation and the current market share of these drugs. It is an up-to-date evaluation of their production and clinical utility.
Doody's Book Reviews
- 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
- highlights the successes, failures and competition in the antibody engineering field from a neutral standpoint
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 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.
ISBN 1 907568 37 9
ISBN-13: 978 1 907568 37 4
October 2012
696 pages 234 x 156mm hardback
£170.00 / US$290.00 / €205.00
Usually dispatched within 24 hours
About the authors
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.
Ms. Lila M. Strohl is a Member of the Association of Medical Illustrators and is a Certified Medical Illustrator. She has worked as the Head of Medical Illustration at St Anthony Medical Center, Columbus, Ohio, as a staff Medical Illustrator in the department of Biomedical Communications at The Ohio State University, USA , and is currently owner of Biomedscapes (Biomedscapes.com), a medical and scientific art company.
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Contents
Introduction to biologics and monoclonal antibodies
- Introduction
- Definitions of biologics
- Recombinant protein therapeutics
- Mabs and Fc fusion proteins (FcFPs)
- General anatomy of a therapeutic IgG Mab
- Naming convention for antibodies from different sources
Value proposition for therapeutic monoclonal antibodies and Fc fusion proteins
- Overview of discovery and development of therapeutic
- Mabs and FcFPs
- Market for Mabs and FcFPs
- Currently and recently approved Mabs and FcFPs
Antibody structure–function relationships
- Introduction
- Constant region structure/function
- Fab structure/function
Fundamental technologies for antibody engineering
- Introduction
- Hybridoma technology – the gateway for therapeutic monoclonal antibodies
- Key recombinant DNA technologies
- Generation of chimeric antibodies
- Display technologies
- Maturity timelines for biologics technologies
Sources of antibody variable chains
- Human antibody gene organization
- Antibody gene rearrangement and diversity in vivo
- Sources of antibody diversity
- Class-switch recombination
- Human variable gene usage
- Variable region selection
- Variable genes from non-human species
- Use of variable genes from humans
Variable chain engineering – humanization and optimization approaches
- Introduction
- Chimerization
- Humanization
- Affinity optimization
Antibody interactions with the immune system
- Introduction
- Human Fcγ receptors
- FcRn and its effect on Mab and FcFP half-life
- Other Fc receptors of importance
- Complement activation
Monoclonal antibody targets and mechanisms of action
- Properties of antibody targets
- Antibody mechanisms of action
- CD20 – example of a target for which multiple MOAs apply
Therapeutic antibody classes
- Human antibody overview
- Human IgG isotypes
- IgM
- IgA
Antibody Fc engineering for optimal antibody performance
- Antibody engineering for decreased or increased effector function
- Current marketed Mabs and clinical candidates with modified Fc
- The effect of human Fc polymorphisms on disease and therapeutic index
- Fc engineering of IgGs to increase effector function
- Fc engineering for silenced effector function
- FcγRIIb-dependent suppression of immune response
- Antibody engineering for modulation of pharmacokinetics
- Tissue targeting
IgG glycans and glyco-engineering
- Introduction to Fc glycosylation
- Non-glycosylated IgGs for lowered effector function
- Low- or non-fucosylated oligosaccharides result in higher ADCC
- Non-sialylated IgG glycans result in increased ADCC
- Sialylated IgG glycans may result in immunosuppressive effects
- High-mannose glycoforms
- Fab glycosylation
Antibody fragments as therapeutics
- Introduction to antibody fragments and alternative formats
- Fab and scFv antibody fragments
- Domain antibodies, including nanobodies, IgNARs, and nanoantibodies
- Antibody size and tissue distribution
- Strategies for half-life extension of antibody fragments
Multiple antibody and multi-specificity approaches
- Introduction
- Serum therapy
- IVIG
- Multi-antibody approaches
- Bispecific antibodies based on IgGs
- Bispecific antibody fragments
FcFPs and similar constructs using Fc
- Introduction
- Receptor-FcFPs
- Traps: multi-ligand binding domains of different receptor chains fused to Fc region
- Soluble protein FcFPs
- Antibody fragment – Fc fusion proteins
- Fc peptide fusions as receptor agonist therapeutics
- Other FcFP structures
- Issues to consider with FcFPs
Antibody-drug conjugates
- Introduction to antibody-drug conjugates
- Overview and anatomy of a typical ADC
- ADC antibodies and targets
- ADC chemical “warheads”
- ADC linkers
- Issues, limitations, and design of ADCs
- Radioimmunoconjugates
- Protein immunotoxins
- ADEPT
- Other ADC-like approaches
Development issues: antibody stability, developability, immunogenicity, and comparability
- Introduction
- Aggregation
- Lack of desired solubility
- Fragmentation
- Post-translational amino acid residue modifications
- Instability and isomerization of disulfide bonds
- Stability at low pH
- Glycosylation issues
- Immunogenicity
- Biocomparability
Interactions of human IgGs with non-human systems
- Introduction
- Non-human primate IgGs and Fcγ receptors
- Mouse IgGs and Fcγ receptors
Cell line development
- Introduction
- Process summary
- Key issues in cell line development
- Choice of cell line
- Mammalian cell lines
- Microbial cells
- Multiple cell lines in single batches
- Gene and vector optimization and selectable markers
- Other industry trends
Issues facing therapeutic monoclonal antibodies
for the future
- Introduction to the future state
- Commoditization of the core underlying technologies
- Impact of follow-on Mabs and FcFPs
- Competition
- The continued need for, and limitation of, novel pre-clinically validated targets
- Payor pressure
- Pipeline in a product concept
- Companion diagnostics and patient segmentation
- Treatment with multiple antibodies and bispecific antibodies
- Mab and FcFP conjugates
- Biopharma in 2020 – the focus on BRIC
- SWOT analysis of therapeutic Mabs and FcFPs
- Epilogue