Therapeutic Antibody Engineering

Erscheinungsjahr 2012
ISBN: 978-1-907568-37-4
Verlag: Elsevier Science & Technology

Buch, Englisch, 696 Seiten, Format (B × H): 164 mm x 241 mm, Gewicht: 1205 g

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.

Autoren/Hrsg.

Strohl, William R.

Strohl, Lila M

Fachgebiete

• Technische Wissenschaften Verfahrenstechnik | Chemieingenieurwesen | Biotechnologie Pharmazeutische Technologie
• Medizin | Veterinärmedizin Medizin | Public Health | Pharmazie | Zahnmedizin Pharmazie
• Wirtschaftswissenschaften Wirtschaftssektoren & Branchen Fertigungsindustrie Pharmaindustrie

Inhaltsverzeichnis

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 Antibody size and tissue distribution

12.5 Strategies for half-life extension of antibod

Über Autor(innen)

Strohl, William R.
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.

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.