Handbook of Therapeutic Antibodies E-Book
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- Herausgeber: Wiley-VCH
- Kategorie: Wissenschaft und neue Technologien
- Sprache: Englisch
Still the most comprehensive reference source on the development, production and therapeutic application of antibodies, this second edition is thoroughly updated and now has 30% more content. Volume 1 covers selection and engineering strategies for new antibodies, while the second volume presents novel therapeutic concepts and antibodies in clinical study, as well as their potential. Volumes 3 and 4 feature detailed and specific information about each antibody approved for therapeutic purposes, including clinical data. This unique handbook concludes with a compendium of marketed monoclonal antibodies and an extensive index. Beyond providing current knowledge, the authors discuss emerging technologies, future developments, and intellectual property issues, such that this handbook meets the needs of academic researchers, decision makers in industry and healthcare professionals in the clinic.
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Seitenzahl: 4819
Veröffentlichungsjahr: 2014
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Table of Contents
Cover
Related Titles
Title Page
Copyright
Quick Reference List of Antibodies by International Nonproprietary Name
Quick Reference List of Antibodies by Brand Name
A Greeting by the Editors
Foreword to the First Edition
Foreword to the Second Edition
List of Contributors
Abbreviations
Appendix: Marketed Monoclonal Antibodies Compendium
Volume I: Def ining the Right Antibody Composition
Chapter 1: Therapeutic Antibodies – from Past to Future
1.1 An Exciting Start – and a Long Trek
1.2 The Gold Rush
1.3 Success and Setbacks
1.4 The Gleaming Horizon
References
Further Reading
Part I: Selecting and Shaping the Antibody Molecule
Chapter 2: Selection Strategies for Monoclonal Antibodies
2.1 Introduction
2.2 Historical Remarks
2.3 Antibody Structure and Function
2.4 Production of Monoclonal Antibodies
2.5 Purification and Modification of Monoclonal Antibodies
2.6 Monoclonal Antibodies for Tumor Therapy
2.7 Outlook
References
Chapter 3: Antibody Phage Display
3.1 Introduction
3.2 Phage Display
3.3 Selection and Screening
3.4 Phage Display Vectors
3.5 Phage Display Libraries
3.6 Construction of Phage Display Libraries
Acknowledgments
References
Chapter 4: Transgenic Animals Derived by DNA Microinjection
4.1 Introduction
4.2 Construction of Human Ig Transloci
4.3 BAC Integration
4.4 Designer Zinc Finger Endonucleases to Silence Endogenous Ig Loci
4.5 Expression Comparison of Fully Human and Chimeric IgH Loci
4.6 Outlook
References
Chapter 5: Humanization Strategies
5.1 Introduction
5.2 History of Humanization
5.3 CDR-Grafting
5.4 The Design Cycle
5.5 Other Approaches to Antibody Humanization
References
Chapter 6: Antibody Affinity
6.1 Introduction
6.2 Affinity Maturation
6.3 Antibody Affinity: Antigen Binding and Potency
6.4 Binding and Potency
In Vitro
6.5 Binding and Potency
In Vivo
6.6 Selection of High-Affinity Antibodies from Hybridoma Cell Lines
6.7 Generation of Antibodies against Soluble Antigens
6.8 Generation of Antibodies against Cell Surface Antigens
6.9 Determination of Antibody Affinity
6.10 Surface Plasmon Resonance
6.11 Other Methods for Determining Antibody Affinity
6.12 Conclusion
References
Chapter 7: Fc Engineering
7.1 Mechanisms of Action of Monoclonal Antibodies
7.2 Modifying Effector Functions
7.3 Modifying Antibodies' Pharmacokinetics
7.4 Summary and Conclusions
References
Chapter 8: Glycosylation of Antibody Molecules
8.1 Introduction
8.2 Overview of the IgG Molecule
8.3 Quaternary Structure of IgG-Fc: The Protein Moiety
8.4 The IgG-Fc Oligosaccharide Moiety
8.5 IgG-Fc Protein/Oligosaccharide Interactions
8.6 Protective Mechanisms Activated by Immune Complexes
8.7 Role of IgG Glycoforms in Recognition by Cellular FγRs
8.8 The Influence of Fucose and Bisecting
N
-Acetylglucosamine on IgG-Fc Activities
8.9 The Influence of Galactosylation on IgG-Fc Activities
8.10 Sialylation of IgG-Fc Oligosaccharides
8.11 Chemo-Enzymatic Synthesis of Novel IgG-Fc Glycans
8.12 Restoration of Functionality to Aglycosylated IgG-Fc
8.13 IgG-Fab Glycosylation
8.14 Conclusion
References
Chapter 9: Bioinformatics Tools for Analysis of Antibodies
9.1 Introduction
9.2 Numbering Schemes for Antibodies
9.3 Definition of the CDRs and Related Regions
9.4 Antibody Sequence Data
9.5 Antibody Structure Data
9.6 Screening New Antibody Sequences
9.7 abYsis – An Integrated Antibody Sequence and Structure Resource
9.8 Antibody Structure Prediction
9.9 Sequence Families
9.10 Summary
References
Websites
Chapter 10: How to Use IMGT® for Therapeutic Antibody Engineering
10.1 Introduction
10.2 Fundamental Information from IMGT-ONTOLOGY Concepts
10.3 IMGT
®
Tools and Databases
10.4 Examples of IMGT
®
Web Resources for Antibody Engineering and Humanization
10.5 Conclusions
Acknowledgments
Abbreviations
References
Website
Part II: Modified Antibodies
Chapter 11: Bispecific Antibodies
11.1 Introduction
11.2 The Generation of Bispecific Antibodies
11.3 Bispecific Antibodies and Retargeting of Effector Cells
11.4 Bispecific Antibodies and Retargeting of Effector Molecules
11.5 Dual Targeting Strategies with Bispecific Antibodies
11.6 Bispecific Antibodies and Somatic Gene Therapy
11.7 Outlook Update
References
Chapter 12: Single-Domain Antibodies: An Overview
12.1 Introduction
12.2 Historical Perspective
12.3 How are sdAbs Isolated?
12.4 Target Space
12.5 Bi-specifics and Targeted Payloads
12.6 Pharmacokinetics/Biodistribution and Half-Life Extension Technologies
12.7 Imaging
12.8 Outlook
Acknowledgments
References
Chapter 13: Antibody–Drug Conjugates: New Frontier in Cancer Therapeutics
13.1 Introduction
13.2 Currently Approved ADCs for Cancer Treatment
13.3 Cytotoxic Compounds in ADCs
13.4 Linkers in ADCs
13.5 Antibody in ADCs
13.6 Conclusions
References
Chapter 14: Antibody-Targeted Drugs: From Chemical Immunoconjugates to Recombinant Fusion Proteins
14.1 Introduction
14.2 Lessons Learned from Chemical Immunoconjugates
14.3 Recombinant Cytotoxic Fusion Proteins
References
Part III: Emerging Technologies
Chapter 15: Emerging Technologies for Antibody Selection
15.1 Introduction
15.2 Display Technologies
15.3 Antibody Libraries
15.4 Antibody Selection and Maturation
In vitro
15.5 Linking Antibodies to mRNA: Ribosome and mRNA Display
15.6 Advantages of Ribosome Display
15.7 Ribosome Display Systems
15.8 Antibody Generation by Ribosome Display
15.9 Summary
References
Chapter 16: Anti-Idiotypic Antibodies
16.1 Introduction
16.2 Basic Concepts
16.3 Physiological Role of Anti-idiotypic Antibodies
16.4 Anti-Idiotypic Antibody Responses
16.5 Anti-Idiotypic Antibodies in Cancer
16.6 Anti-idiotypic Antibodies in Other Diseases
16.7 Concluding Remarks
References
Chapter 17: Non-Antibody Scaffolds as Alternative Therapeutic Agents
17.1 Introduction
17.2 Motivation for Therapeutic Use of Alternative Binding Proteins
17.3 Single Domain Immunoglobulins
17.4 Scaffold Proteins Presenting a Contiguous Hypervariable Loop Region
17.5 Scaffold Proteins for Display of Individual Extended Loops
17.6 Scaffold Proteins Providing a Rigid Secondary Structure Interface
17.7 Non-Antibody Scaffolds Stepping into the Clinic
17.8 Conclusions and Outlook: Therapeutic Potential and Ongoing Developments
References
Chapter 18: Antibody-Directed Enzyme Prodrug Therapy (ADEPT)
18.1 Introduction and Basic Principles of ADEPT
18.2 Pre-clinical Studies
18.3 Clinical Studies
18.4 Immunogenicity
18.5 Important Considerations/Outlook
Acknowledgments
Abbreviations
References
Chapter 19: Engineered Antibody Domains as Candidate Therapeutics
19.1 Introduction
19.2 eAd Structure and Function
19.3 eAd Libraries
19.4 eAds against HIV-1
19.5 eAds Targeting Cancer
19.6 eAds against Inflammation
19.7 eAds against Hematological Disorders
19.8 Conclusions
Acknowledgments
References
Chapter 20: Chimeric Antigen Receptors – “CARs”
20.1 Introduction
20.2 Chimeric Antigen Receptors – “CARs”
20.3 Preclinical Studies
20.4 Therapeutic Considerations
20.5 Perspectives
20.6 Conclusions
References
Chapter 21: Emerging Alternative Production Systems
21.1 Introduction
21.2 Production Systems
21.3 Outlook
Abbreviations
References
Volume II: Clinical Development of Antibodies
Part IV: The Way into the Clinic
Chapter 22: Process Development and Manufacturing of Therapeutic Antibodies
22.1 Introduction
22.2 Upstream Processing
22.3 Downstream Processing
22.4 Formulation Development
22.5 Commercial Manufacturing Processes
22.6 Analytics
22.7 Overall Process Development Strategies and Outlook
Acknowledgments
References
Chapter 23: The Immunogenicity of Therapeutic Antibodies
23.1 Introduction
23.2 Immunogenicity and the Immune System
23.3 Factors Influencing Immunogenicity
23.4 Clinical Consequences of Immunogenicity of Abs
23.5 Bioanalytical Assessment of ADAs against Therapeutic Antibodies
23.6 Immunogenicity Prediction Tools
23.7 Reduction of Immunogenicity of Abs
23.8 A Look into the Future – The Rise of Antibody-Based Drugs
23.9 Conclusions
References
Chapter 24: Biosimilar Monoclonal Antibodies
24.1 Introduction
24.2 EU Approach to Biosimilars
24.3 US Biosimilars
24.4 Follow-On Monoclonal Antibodies in Emerging Markets
24.5 Technical Development and Analytical Characterization of Biosimilar Monoclonal Antibodies
24.6 Non-Clinical and Clinical Development of Biosimilar Monoclonal Antibodies/Pharmacovigilance and Risk Management
Acknowledgments
Abbreviations
References
Chapter 25: Patent Issues Relating to Therapeutic Antibodies
25.1 Why Patents Matter
25.2 Types of Patent Protection in the Field of Therapeutic Antibodies
25.3 Freedom to Operate
25.4 Protecting New Developments
25.5 Management of Own and Third-Party Patents
25.6 Patent Exploitation Options and Business Models
25.7 Outlook
25.8 Reference Materials and Further Reading
Part V: Therapeutic Antibody Pipeline
Chapter 26: Monoclonal Antibody Cancer Treatments in Phase III Clinical Trials
26.1 Introduction
26.2 Antibodies for Use in Lymphoma and Related Diseases
26.3 Anti-EpCAM Antibodies: A Lesson in History and What Remains
26.4 Antibodies Against Epithelial Growth Factor Targets
26.5 Insulin-Like Growth Factor Type I Receptor Antibodies
26.6 Antibodies for Use in Renal Cell Carcinoma
26.7 Antibodies for Use in Ovarian Cancer
26.8 Blockage of Immunological Checkpoints
26.9 Miscellaneous Diseases and Targets
26.10 Summary
References
Chapter 27: Antibodies in Cancer Treatment: Early Clinical Development
27.1 Introduction
27.2 Harnessing Innate Immunity
27.3 Alteration of Intracellular Signaling
27.4 Immunoconjugates
27.5 The Three U's: Mechanisms of Unique, Unclear, or Unknown Function
27.6 Summary
References
Chapter 28: Targeting Angiogenesis by Therapeutic Antibodies
28.1 Introduction
28.2 Therapeutic Antibodies
28.3 Conclusion
Abbreviations
References
Chapter 29: Antibodies in Phase III Studies for Immunological Disorders
29.1 Introduction
29.2 Antibody Targets in Phase III Trials
29.3 Summary
References
Chapter 30: Monoclonal Antibodies in Phase 1 and 2 Studies for Immunological Disorders
30.1 Introduction
30.2 General Overview of the Immune System and Key Pathways Driving Inflammatory Diseases
30.3 Review of the Major Inflammatory Diseases Targeted by mAbs, Goals of Current Therapies and How These Might Be Met by Existing and Emerging Biologics
30.4 Mechanisms of Target Modulation Utilized by Monoclonal Antibodies
30.5 Optimizing mAbs for Efficacy and Safety
30.6 Summary
References
Chapter 31: MAbs Targeting Soluble Mediators in Phase 1 and 2 Clinical Studies Immunological Disorders
31.1 Introduction
References
Chapter 32: T Cell Inhibitors in Phase 1 and 2 Clinical Studies for Immunological Disorders
32.1 Introduction
32.2 T-Cell Inhibitors
32.3 Anti-T-Cell Costimulators
References
Chapter 33: B-Cell Inhibitors in Phase 1 and 2 Clinical Studies for Immunological Disorders
33.1 Introduction
33.2 Anti-CD19
33.3 Anti-BAFF (Blys)
33.4 Anti-CD20
References
Chapter 34: Inhibitors of Leukocyte Adhesion and Migration in Phase 1 and 2 Clinical Studies for Immunological Disorders
34.1 Introduction
34.2 Inhibitors of Leukocyte Adhesion and Migration
References
Chapter 35: Toll-Like Receptor Inhibitors in Phase 1 and 2 Clinical Studies for Immunological Disorders
35.1 Introduction
35.2 Toll-Like Receptor Inhibitors
References
Chapter 36: IgE Inhibitors in Phase 1 and 2 Clinical Studies for Immunological Disorders
36.1 Introduction
36.2 IgE Inhibitors
References
Chapter 37: Complement Inhibitors in Phase 1 and 2 Clinical Studies for Immunological Disorders
37.1 Introduction
37.2 Complement Inhibitors
References
Chapter 38: mAbs Targeting Apoptosis, Angiogenesis Inhibitors, and Other mAbs in Phase 1 and 2 Clinical Studies for Immunological Disorders
38.1 mAbs Targeting Apoptosis
38.2 Angiogenesis Inhibitors
38.3 Other mAbs
References
Chapter 39: In vitro Studies and Clinical Trials about Monoclonal Antibodies Used in Infectiology
39.1 Introduction and Infectious Context
39.2 Historical of Antibodies Used in Infectiology and Previous Clinical Trials
39.3 General Mechanisms of Action
39.4 Mode of Production of Anti-Infectious Antibodies
39.5 Anti-Infectious Monoclonal Antibodies Against Bacteria and Associated Toxins
39.6 Viral Diseases and Anti-Infectious Monoclonal Antibodies
39.7 Perspectives and Future Development of Antimycotic Monoclonal Antibodies
39.8 Conclusion
Acknowledgments
Author Contributions
Funding
Transparency Declarations Sections and Conflicts of Interest
References
Chapter 40: Immunotherapeutics for Neurological Disorders
40.1 Introduction
40.2 Alzheimer's Disease
40.3 Parkinson's Disease and Dementia with Lewy Bodies
40.4 Huntington's Disease
40.5 Amyotrophic Lateral Sclerosis
40.6 Transmissible Spongiform Encephalopathies
40.7 Conclusion
Acknowledgments
References
Part VI: Gaining Marketing Approval
Chapter 41: Regulatory Considerations in the Development of Monoclonal Antibodies for Diagnosis and Therapy*
41.1 Introduction
41.2 Regulatory Authority
41.3 Chemistry, Manufacturing, and Controls Considerations
41.4 Considerations for Nonclinical Testing
41.5 Immunogenicity
41.6 Conclusions
Acknowledgments
References
Chapter 42: Regulatory Review: Clinical to Market Transition
42.1 Introduction
42.2 General Considerations for the Clinical Development of mAbs
42.3 The Need for Regulatory Validation of the Development Program
42.4 The Approach of Agencies for Clinical Review of mAb
42.5 Strategic Regulatory Options for Rapid Market Access
42.6 Pivotal Clinical Trials for mAb
42.7 Specific Considerations for Early Development Clinic Studies of mAb
References
Chapter 43: Monoclonal Antibody Nomenclature for Clinical Studies (USA)1
43.1 Elements of a Name
43.2 Sequence of Stems and Infixes
43.3 Target/Disease Class Infix
43.4 USAN Modified Designations for Monoclonal Antibodies
43.5 Required Application Information
Volume III: Approved Therapeutic Antibodies
Part VII: Approved Therapeutic Antibodies
Chapter 44: Oligoclonal and Polyclonal Antibody Preparations
44.1 Introduction
44.2 Oligoclonal Antibodies
44.3 General Questions/Concerns
44.4 Uses/Applications of Oligoclonal Antibodies
44.5 Infectious Disease
44.6 FDA/Regulatory Considerations
44.7 Polyclonal Antibodies
44.8 Production of Polyclonal Antibodies
44.9 Immunogen Properties and Preparations
44.10 Carrier Proteins for Immunogen Preparation
44.11 Choice of Animal
44.12 Adjuvants
44.13 Route of Injection
44.14 Collecting and Processing of Blood
44.15 Antibody Purification
44.16 Polyclonal Antibody Derives Therapeutics (Clinical Utility)
44.17 Recombinant Polyclonal Antibodies
44.18 Summary
References
Chapter 45: Adalimumab (Humira®)
45.1 Overview
45.2 Basic Principles of Clinical Use
45.3 Safety
45.4 Use in Approved Indications
45.5 Clinical Studies in Intestinal Behçet Disease
45.6 Clinical Studies in Uveitis
45.7 Clinical Studies in Hidradenitis Suppurativa
45.8 Early-Stage Clinical Studies in Sarcoidosis
References
Chapter 46: Alemtuzumab (Lemtrada, MabCampath)1
46.1 Overview
46.2 Basic Principles
46.3 Antibody Features and Production
46.4 Molecular Target and Target Expression
46.5 Mechanism of Cell Lysis
46.6 Immunogenicity and Antiglobulin Response
46.7 Pharmacokinetic Studies
46.8 Clinical Studies in Chronic Lymphocytic Leukemia (CLL)
46.9 Clinical Studies in Multiple Sclerosis
46.10 Clinical Studies in Other Indications
References
Chapter 47: Basiliximab (Simulect®) and Daclizumab (Zenapax®)
47.1 Background
47.2 Clinical Use in Human Organ Transplantation
47.3 Clinical Use of IL-2R Antibodies in Non-organ Transplant Conditions
47.4 Conclusion
References
Chapter 48: Belimumab (Benlysta®)
48.1 Introduction
48.2 Basic Principles
48.3 Clinical Aspects of Belimumab Therapy
48.4 Summary
List of abbreviations
References
Chapter 49: Brentuximab Vedotin (Adcetris®) for the Treatment of CD30-Positive Hematologic Malignancies
49.1 Introduction
49.2 CD30
49.3 Preclinical Activity of Brentuximab Vedotin
49.4 Clinical Development of Brentuximab Vedotin
49.5 Future Perspectives
Acknowledgments
References
Chapter 50: Canakinumab (ILARIS®)
50.1 Introduction
50.2 Production, Pharmacology, and Pharmacokinetics of Canakinumab
50.3 Clinical Trials
50.4 Outlook and Summary
References
Chapter 51: Catumaxomab (Removab) – Trifunctional Antibodies: Combining Direct Tumor Cell Killing with Therapeutic Vaccination
51.1 Introduction
51.2 Manufacturing of trAbs
51.3 The Mode of Action of trAbs in Tumor Treatment
51.4 From Bench to Bedside with the Triomab
®
trAb Family
51.5 Potential Biomarkers Along trAb Treatment Concept
51.6 Concluding Remarks
Acknowledgments
References
Chapter 52: Cetuximab (Erbitux)
52.1 Nature, Role in Disease, Biology of the Target
52.2 Origin and Development of Erbitux
52.3 Mechanism of Action
52.4 Preclinical and Clinical Results
52.5 Production
52.6 Cetuximab in Clinics
52.7 Outlook
References
Websites
Chapter 53: Denosumab (Prolia
®
)
53.1 Introduction
53.2 Clinical Studies
53.3 Guidelines of the FDA (Website of FDA) for Denosumab (Prolia)
53.4 Summary and Outlook
References
Websites
Chapter 54: Efalizumab (Raptiva)
54.1 Introduction
54.2 Development and Characterization of the Antibody
54.3 Efalizumab in the Treatment of Psoriasis
54.4 Pharmacology and Toxicology of Efalizumab
54.5 Clinical Development of Efalizumab
54.6 Health-Related Quality of Life (HRQoL)
54.7 Safety and Tolerability
54.8 Efalizumab: Reassessment of Benefit–Risk Ratio and Suspension of Marketing Authorization
References
Chapter 55: Calicheamicin Conjugates: Gemtuzumab Ozogamicin (Mylotarg), Inotuzumab Ozogamicin
55.1 Introduction
55.2 Target Antigen Selection in Therapy with ADC
55.3 Conjugate Design/Preclinical Activity
55.4 Mechanisms of Action
55.5 Potential Mechanisms of Resistance
55.6 Clinical Trials
55.7 Summary and Conclusions
References
Chapter 56: Golimumab (Simponi®)
56.1 Introduction
56.2 Characterization and Preclinical Evaluation
56.3 First-in-Humans Study
56.4 Pivotal Clinical Studies
56.5 Market Competitors
References
Chapter 57: Yttrium-90 Ibritumomab Tiuxetan (Zevalin
®
)
57.1 Introduction
57.2 Basic Principles of Radioimmunotherapy
57.3 Development and Advantages of
90
Y-Ibritumomab Tiuxetan
57.4 Preclinical and Clinical Results
57.5 Outlook
References
Chapter 58: Infliximab (Remicade®)
58.1 Antibody Characteristics
58.2 Preclinical Characterization
58.3 Pharmacokinetics
58.4 Clinical Response
58.5 Safety
58.6 Summary
References
Chapter 59: Ipilimumab (Yervoy®)
59.1 Introduction
59.2 Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4)
59.3 Ipilimumab, Mechanism of Action
59.4 Pharmacokinetics
59.5 Melanoma
59.6 Prostate Cancer
59.7 Lung Cancer
59.8 Patterns of Response with Ipilimumab (Immune-Related Response Criteria)
59.9 Adverse Events
59.10 Conclusions
References
Chapter 60: Muromonab-CD3 (Orthoclone OKT®3)
60.1 Introduction
60.2 Production of mAbs
60.3 Pharmacology of Muromonab-CD3
60.4 Therapeutic Use
60.5 Cytokine Release Syndrome
60.6 Consequences of Immunosuppression
60.7 Withdrawal from the Market
References
Chapter 61: Nimotuzumab: A Humanized Anti-EGFR Antibody
61.1 Overview
61.2 Head and Neck
61.3 Glioma
61.4 Pediatric Glioma
61.5 Esophageal and Gastric Cancer
61.6 Pancreatic Cancer
61.7 Non-Small Cell Lung Cancer (NSCLC)
61.8 Concluding Remarks
References
Chapter 62: Obinutuzumab (Gazyva®), a Novel Glycoengineered Type II CD20 Antibody for the Treatment of Chronic Lymphocytic Leukemia and Non-Hodgkin's Lymphoma
62.1
In vitro
Mechanism of Action of Type I and Type II CD20 Antibodies
62.2 Generation of Obinutuzumab
62.3 Obinutuzumab is a Classical Type II CD20 Antibody
62.4 The Epitope Recognized by Obinutuzumab
62.5 CDC Activity of Obinutuzumab
62.6 Direct Cell Death Induction by Obinutuzumab
62.7 Glycoengineering of Obinutuzumab
62.8
In vitro
NK Cell and Neutrophil ADCC and Macrophage ADCP Activity of Obinutuzumab
62.9
Ex vivo
Whole Blood B-Cell Depletion by Obinutuzumab
62.10
In vivo
Activity of Obinutuzumab in Xenograft Models
62.11
In vivo
Activity of Obinutuzumab in Combination with Chemotherapy, Bcl-2, and MDM2 Inhibitors
62.12 B-Cell Depletion by Obinutuzumab in Cynomolgus Monkeys
62.13 Conclusion from Nonclinical Pharmacology Studies with Obinutuzumab
62.14 Clinical Experiences with Obinutuzumab
62.15 Early Clinical Experience with Obinutuzumab in B-Cell Lymphoma
62.16 Phase Ib and II Experience with Obinutuzumab in B-Cell Lymphoma
62.17 Phase III Studies with Obinutuzumab in B-Cell Lymphoma
62.18 Obinutuzumab in CLL: Early Experience and Ongoing Phase II Studies
62.19 Phase III Experience with Obinutuzumab: The CLL11 Trial
References
Volume IV: Approved Therapeutic Antibodies and in vivo Diagnostics
Chapter 63: Ofatumumab (Arzerra®): a Next-Generation Human Therapeutic CD20 Antibody with Potent Complement-Dependent Cytotoxicity
63.1 Introduction and Preliminary Comments
63.2 Physical and Immunochemical Characteristics of OFA Compared to RTX
63.3 Functional Characterizations
63.4 CD20: It Is certainly a Good Target, but How Well Characterized Is It?
63.5 Key Results of Clinical Trials with OFA
63.6 Summary and Future Directions
Abbreviations
63.7 Disclosures
References
Chapter 64: Omalizumab (Xolair) – Anti-Immunoglobulin E Treatment in Allergic Diseases
64.1 Introduction
64.2 The Biology of the IgE Molecule
64.3 IgE Receptors
64.4 Cell Distribution of IgE
64.5 Physiologic and Pathophysiologic Significance of IgE
64.6 The Concept of Anti-IgE-Based Treatment
64.7 Construction of the Monoclonal Anti-IgE Molecule
64.8 Efficacy
64.9 Anti-Inflammatory Effects of Omalizumab
64.10 Pharmacological Properties of Omalizumab
64.11 Adverse Effects
64.12 Indications
64.13 Contraindications
64.14 Preparation for Use
64.15 Administration
64.16 Dosing of Omalizumab
64.17 Response to Treatment
64.18 Assessment of Therapeutic Response
64.19 Monitoring of Therapy
64.20 Drug Interactions
64.21 Pregnancy and Lactation
64.22 Cost
64.23 Non-approved Diseases
64.24 Conclusions
Acknowledgments
References
Websites
Chapter 65: Palivizumab (Synagis®)
65.1 Nature, Role in Disease, and Biology of the Target
65.2 Origin, Engineering, and Humanization of the Antibody
65.3 Mechanism of Action and Preclinical Results
65.4 Production, Downstream Processing, and Galenics of the Antibody
65.5 Summary of Results from Clinical Studies
65.6 Indications and Usage
65.7 Clinical Reports after Approval
65.8 Protective Efficacy as a Function of Palivizumab Serum Concentration?
65.9 Postmarketing Experience with Regard to Adverse Events (AEs)
65.10 Toward Improved Versions of Palivizumab
65.11 Summary
Acknowledgments
Abbreviations
References
Chapter 66: Panitumumab (Vectibix®): A Treatment for Metastatic Colorectal Cancer
66.1 Introduction
66.2 Panitumumab (Vectibix)
66.3 Results from Clinical Studies
66.4 Summary and Outlook
References
Chapter 67: Pertuzumab (Perjeta®)
67.1 HER2-Positive Breast Cancer
67.2 Mechanisms of Trastuzumab Resistance
67.3 Preclinical Development
67.4 Pertuzumab Clinical Development
67.5 Pertuzumab Cardiac Safety Profile
References
Chapter 68: Ranibizumab (Lucentis): a New Anti-Angiogenic Treatment in Ophthalmology
68.1 Introduction
68.2 Ranibizumab: Clinical Studies in Retinal Disorders
68.3 Other Molecules with Anti-VEGF Effect of Clinical Use in Retinal Disorders
References
Chapter 69: Raxibacumab, Human Monoclonal Antibody against Anthrax Toxin
69.1 Introduction
69.2 Development of Raxibacumab
69.3 Demonstration of Effectiveness under the Animal Rule
69.4 Safety
69.5 Dosing
69.6 Indication
69.7 Conclusion
Abbreviations
References
Chapter 70: Rituximab (Rituxan®)
70.1 Introduction
70.2 Rituximab Clinical Data in B-Cell Lymphoma
70.3 Rituximab in Autoimmune Disorders
70.4 Development of a Subcutaneous Rituximab Formulation (Rituximab SC) in B-Cell Lymphoma and CLL
70.5 Summary and Conclusions
References
Websites
Chapter 71: Tocilizumab (Actemra®)
71.1 Introduction
71.2 Biological Activities and Signaling of IL-6
71.3 Targeting IL-6 with Monoclonal Antibodies
71.4 Targeting IL-6 in Rheumatoid Arthritis
71.5 Targeting IL-6 in Systemic-Onset Juvenile Idiopathic Arthritis
71.6 Targeting IL-6 in Castleman's Disease
71.7 Other Indications
71.8 Adverse Events Associated with Targeting the IL-6 Receptor
71.9 Current State of Play
References
Chapter 72: Trastuzumab (Herceptin®) and Ado-Trastuzumab Emtansine (Kadcyla®): Treatments for HER2-Positive Breast Cancer
72.1 Introduction
72.2 Metastatic Breast Cancer
72.3 Early Breast Cancer
72.4 Cardiac Adverse Events
72.5 Infusion-Related Reactions
72.6 Age Considerations
72.7 Patient Considerations
72.8 Dosing/Scheduling
72.9 Ado-Trastuzumab Emtansine (T-DM1), Trade Name Kadcyla
72.10 Safety and Side Effects
72.11 FDA Approval
72.12 Conclusions
References
Chapter 73: Ustekinumab (Stelara®)
73.1 Introduction
73.2 Psoriasis
73.3 Psoriatic Arthritis
73.4 Crohn's Disease
73.5 Multiple Sclerosis
73.6 Meta Analyses on Long-Term Use
73.7 Ongoing Studies, New Indications, and Outlook
References
Chapter 74: Abciximab (Reopro®), Bevacizumab (Avastin®), Certolizumab Pegol (Cimzia®), Eculizumab (Soliris®), Natalizumab (Tysabri®)
74.1 Abciximab (Reopro)
74.2 Bevacizumab (Avastin)
74.3 Certolizumab Pegol (Cimzia)
74.4 Eculizumab (Soliris)
74.5 Natalizumab (Tysabri)
References
Chapter 75: Itolizumab (Alzumab®), Mogamulizumab (Poteligeo®), and Tositumomab (Bexxar®)
75.1 Itolizumab (Alzumab)
75.2 Mogamulizumab (Poteligeo)
75.3 Tositumomab; Iodine
131
I Tositumomab (Bexxar)
References
Further Reading
Information Sources
Part VIII: In vivo Diagnostics
Chapter 76: Radiolabeled Antibodies for Diagnostic Imaging
76.1 Introduction
76.2 Oncology
76.3 Cardiology
76.4 Infection
76.5 Summary
References
Index
End User License Agreement
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Guide
Cover
Table of Contents
Foreword to the First Edition
Volume I: Def ining the Right Antibody Composition
Part I: Selecting and Shaping the Antibody Molecule
Chapter 1: Therapeutic Antibodies – from Past to Future
List of Illustrations
Figure 1.1
Figure 1.2
Figure 1.3
Figure 2.1
Figure 2.2
Figure 2.3
Figure 2.4
Figure 2.5
Figure 2.6
Figure 2.7
Figure 3.1
Figure 4.1
Figure 4.2
Figure 4.3
Figure 4.4
Figure 4.5
Figure 4.6
Figure 4.7
Figure 5.1
Figure 6.1
Figure 6.2
Figure 6.3
Figure 6.4
Figure 7.1
Figure 7.2
Figure 7.3
Figure 8.1
Figure 8.2
Figure 8.3
Figure 10.1
Figure 10.2
Figure 10.3
Figure 10.4
Figure 10.5
Figure 10.6
Figure 10.7
Figure 10.8
Figure 10.9
Figure 10.10
Figure 11.1
Figure 11.2
Figure 11.3
Figure 11.4
Figure 11.5
Figure 11.6
Figure 11.7
Figure 11.8
Figure 11.9
Figure 11.10
Figure 12.1
Figure 12.2
Figure 12.3
Figure 12.4
Figure 13.1
Figure 13.2
Figure 13.3
Figure 13.4
Figure 13.5
Figure 15.1
Figure 15.2
Figure 15.3
Figure 16.1
Figure 16.2
Figure 17.1
Figure 17.2
Figure 18.1
Figure 19.1
Figure 19.2
Figure 19.3
Figure 19.4
Figure 20.1
Figure 20.2
Figure 20.3
Figure 20.4
Figure 22.1
Figure 22.2
Figure 22.3
Figure 22.4
Figure 22.5
Figure 22.6
Figure 22.7
Figure 22.8
Figure 22.9
Figure 22.10
Figure 22.11
Figure 22.12
Figure 22.13
Figure 23.1
Figure 23.2
Figure 23.3
Figure 24.1
Figure 24.2
Figure 24.3
Figure 24.4
Figure 24.5
Figure 24.6
Figure 24.7
Figure 25.1
Figure 16.1
Figure 28.1
Figure 28.2
Figure 41.1
Figure 46.1
Figure 46.2
Figure 46.3
Figure 46.4
Figure 46.5
Figure 46.6
Figure 46.7
Figure 46.8
Figure 49.1
Figure 49.2
Figure 49.3
Figure 49.4
Figure 50.1
Figure 50.2
Figure 50.3
Figure 50.4
Figure 50.5
Figure 51.1
Figure 51.2
Figure 51.3
Figure 51.4
Figure 51.5
Figure 51.6
Figure 52.1
Figure 53.1
Figure 55.1
Figure 55.2
Figure 55.3
Figure 55.4
Figure 57.1
Figure 57.2
Figure 59.1
Figure 60.1
Figure 62.1
Figure 62.2
Figure 62.3
Figure 62.4
Figure 63.1
Figure 63.2
Figure 63.3
Figure 63.4
Figure 63.5
Figure 63.6
Figure 63.7
Figure 63.8
Figure 63.9
Figure 63.10
Figure 64.1
Figure 64.2
Figure 64.3
Figure 64.4
Figure 64.5
Figure 64.6
Figure 64.7
Figure 64.8
Figure 64.9
Figure 64.10
Figure 64.11
Figure 64.12
Figure 64.13
Figure 64.14
Figure 64.15
Figure 64.16
Figure 64.17
Figure 65.1
Figure 65.2
Figure 65.3
Figure 65.4
Figure 65.5
Figure 66.1
Figure 68.1
Figure 68.2
Figure 68.3
Figure 68.4
Figure 70.1
Figure 70.2
Figure 70.3
Figure 70.4
Figure 70.5
Figure 70.6
Figure 70.7
Figure 70.8
Figure 70.9
Figure 70.10
Figure 70.11
Figure 70.12
Figure 70.13
Figure 72.1
Figure 72.2
Figure 72.3
Figure 72.4
Figure 72.5
Figure 72.6
Figure 72.7
Figure 72.9
Figure 72.8
Figure 72.10
Figure 72.11
Figure 73.1
Figure 76.1
Figure 76.2
Figure 76.3
Figure 76.4
Figure 76.5
Figure 76.6
Figure 76.7
Figure 76.8
Figure 76.9
List of Tables
Table 1.1
Table 1.2
Table 2.1
Table 3.1
Table 3.2
Table 3.3
Table 5.1
Table 5.2
Table 7.2
Table 7.1
Table 7.3
Table 9.1
Table 9.2
Table 9.3
Table 9.4
Table 9.5
Table 10.1
Table 10.2
Table 10.3
Table 11.1
Table 11.2
Table 12.1
Table 12.2
Table 13.1
Table 13.2
Table 14.1
Table 14.2
Table 14.3
Table 15.1
Table 17.1
Table 17.2
Table 17.3
Table 17.4
Table 19.1
Table 20.1
Table 20.2
Table 20.3
Table 20.4
Table 21.1
Table 22.1
Table 22.2
Table 22.3
Table 22.4
Table 22.5
Table 22.6
Table 22.7
Table 22.8
Table 23.1
Table 23.2
Table 23.3
Table 23.4
Table 23.5
Table 24.1
Table 24.2
Table 26.1
Table 29.1
Table 29.2
Table 29.3
Table 29.4
Table 29.5
Table 29.6
Table 29.7
Table 29.8
Table 29.9
Table 29.10
Table 29.11
Table 29.12
Table 30.1
Table 30.2
Table 41.1
Table 41.2
Table 42.1
Table 42.2
Table 44.1
Table 44.2
Table 45.1
Table 46.1
Table 46.2
Table 46.3
Table 46.4
Table 46.5
Table 46.6
Table 46.7
Table 47.1
Table 47.2
Table 47.3
Table 48.1
Table 49.1
Table 49.2
Table 51.1
Table 51.2
Table 51.3
Table 51.4
Table 52.1
Table 52.2
Table 53.1
Table 56.1
Table 57.1
Table 57.2
Table 57.3
Table 57.4
Table 59.1
Table 59.2
Table 59.3
Table 59.4
Table 60.1
Table 60.2
Table 60.3
Table 60.4
Table 60.5
Table 62.1
Table 62.2
Table 62.3
Table 63.1
Table 63.2
Table 64.1
Table 64.2
Table 64.3
Table 64.4
Table 64.5
Table 64.6
Table 64.7
Table 64.8
Table 64.9
Table 64.10
Table 64.11
Table 65.1
Table 65.2
Table 65.3
Table 66.1
Table 67.1
Table 69.1
Table 70.1
Table 70.2
Table 70.3
Table 70.4
Table 70.5
Table 70.6
Table 70.7
Table 70.8
Table 71.1
Table 71.2
Table 71.3
Table 72.1
Table 72.2
Table 72.3
Table 73.1
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Edited by Stefan Dübel and Janice M. Reichert
Handbook of Therapeutic Antibodies
Volume I: Defining the Right Antibody Composition
Second Edition
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Handbook of Therapeutic Antibodies
Volume II: Clinical Development of Antibodies
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Editors
Prof. Dr. Stefan Dübel
Technische Universität Braunschweig
Institute of Biochemistry
Biotechnology and Bioinformatics
Spielmannstr. 7
38106 Braunschweig
Germany
Dr. Janice M. Reichert
Reichert Biotechnology Consulting LLC
Prospect Street 247
Framingham, MA
USA
Cover
Antibodies have become standard therapy in many therapeutic areas including cancer, inflammation, osteoporosis, autoimmune, cardiovascular, ophthalmic and infectious diseases. Early successes in the treatment of leukemia and lymphoma by rituximab and alemtuzumab spawned the development of ofatumumab and obinutuzumab, antibodies that kill tumor cells more potently via diverse mechanisms. The cover is an artist's impression of lymphocytic leukemia cells under therapeutic antibody attack. The image was developed by Joost M. Bakker, www.scicomvisuals.com.
Limit of Liability/Disclaimer of Warranty: While the publisher and author have used their best efforts in preparing this book, they make no representations or warranties with respect to the accuracy or completeness of the contents of this book and specifically disclaim any implied warranties of merchantability or fitness for a particular purpose. No warranty can be created or extended by sales representatives or written sales materials. The Advice and strategies contained herein may not be suitable for your situation. You should consult with a professional where appropriate. Neither the publisher nor authors shall be liable for any loss of profit or any other commercial damages, including but not limited to special, incidental, consequential, or other damages.
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