Ulteriori informazioni
Informationen zum Autor 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. Klappentext Therapeutic antibody engineering examines all aspects of engineering monoclonal antibodies to make more competitive antibodies and how the various genetic engineering approaches will affect candidates of the future. Zusammenfassung Therapeutic antibody engineering examines all aspects of engineering monoclonal antibodies to make more competitive antibodies and how the various genetic engineering approaches will affect candidates of the future. Inhaltsverzeichnis Introduction to biologics and monoclonal antibodies; Value proposition for therapeutic monoclonal antibodies and Fc fusion proteins; Antibody structure - function relationships; Fundamental technologies for antibody engineering; Sources of antibody variable chains; Variable chain engineering - humanization and optimization approaches; Antibody interactions with the immune system; Monoclonal antibody targets and mechanisms of action; Therapeutic antibody classes; Antibody Fc engineering for optimal antibody performance; IgG glycans and glyco-engineering; Antibody fragments as therapeutics; Multiple antibody and multi-specificity approaches; FcFPs and similar constructs using Fc; Antibody-drug conjugates; Development issues: antibody stability! developability! immunogenicity! and comparability; Interactions of human IgGs with non-human systems; Cell line development; Issues facing therapeutic monoclonal antibodies for the future.
Sommario
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 structureâ?"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 â?" 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 Fc? 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 Fc?RIIb-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
Relazione
"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 Reviews
