Therapeutic Antibodies

237 Pages·1995·7.6 MB·English

by  J. Landon

J.
Landon and T. Chard (Eds)
Therapeutic Antibodies
With 17 Figures
Springer-Verlag
London Berlin Heidelberg New York
Paris Tokyo Hong Kong
Barcelona Budapest
John Landon, MD, FRCP
Department of Chemical Pathology, St Bartholomew's Hospital
Medical College, Charterhouse Square, London ECIM 7BQ, UK
Tim Chard, MD, FRCOG
Joint Academic Unit of Obstetrics, Gynaecology and
Reproductive Physiology, St Bartholomew's Hospital Medical
College, West Smithfield, London EClA 7BE, UK
Cover illustration: Ch. 2, Fig. 2. The structure of IgM.
ISBN-13: 978-1-4471-1939-5 e-ISBN-13: 978-1-4471-1937-1
001: 10.1007/978-1-4471-1937-1
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© Springer-Verlag London Limited 1995
Softcover reprint of the hardcover in 1s t edition 1995
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Contents
I>reface. . . ix
Contributors xi
1 An Introduction to the Clinical Applications
of Antibodies
l. Landon, T. Chard and R. E. Coxon 1
History. . . . . . . . . . . . . . 1
Types and Sources of Antibodies 3
Diagnostic Applications . . . . . 7
Therapeutic Applications . . . . 10
Potential Side-Effects ..... 21
Anticipated Developments and Conclusions 28
References ................. 31
2 Biology of the Immune Response
T. Poulton and F. Hay 33
Introduction . . . . . . 33
Innate Immune System 33
Adaptive Immunity . . 35
A Typical Immune Response 38
Immunoglobulin Structure and Function 39
References ............... 45
3 Antibody Production in the Hen
l. Landon, l.A. Woolley and C. McLean 47
Summary ................. 47
Background ............... 48
Comparison of Avian and Mammalian Antibody
Production. . . . . . . . . . . . . . . . . . 55
Uses of Avian Antibodies. . . . . . . . . . . 57
Alternatives to Avian Antibodies for Therapy 65
References . . . . . . . . . . . . . . 66
4 Catalytic Antibodies
G. Gallacher. 69
Introduction . . . . 69
vi Therapeutic Antibodies
Catalysis via Transition-State Complementarity. 69
Antibody-Catalysed Hydrolysis of Labile Esters 70
Hydrolysis of More-Stable Compounds 75
Catalysis via Other Strategies . . . . . . . . . 76
Catalysis of Other Types of Reaction . . . . . 79
Polyclonal Catalytic Antibodies . . . . . . . . 81
Developing Therapeutic Catalytic Antibodies. 83
Conclusion. 86
References 86
5 Immunotherapy for Drug Toxicity
A.J. Heath 89
Introduction 89
Digoxin .. 91
Colchicine . 102
Tricyclic Antidepressants 104
References ...... . 106
6 Therapeutic Antibodies to Snake Venoms
R.D.G. Theakston and D.C. Smith 109
History ................. . 109
Standard Methods of Antivenom Production 109
Different Types of Available Antivenams. . 110
Antivenom Reactions ......... . 111
Methods of Antivenom Potency Assessment 112
Recent Developments in Antivenom Production 115
Conclusions 128
References .................. . 128
7 Therapeutic Antibodies to Tumours
l.A. Ledermann ........ . 135
Introduction . . . . . . . . . . . . . . . . . 135
Cell Surface Targets for Antibody Therapy . 136
Biodistribution of Antibodies . . 136
Therapeutic Strategies. . . . . . 138
Limitations of Antibody Therapy 145
Conclusions 148
References ........... 149
8 Therapeutic Antibodies to Microorganisms
P.L. Yap ................ 153
Introduction . . . . . . . . . . . . . . . . 153
Antibody Preparations Available for Prophylaxis
and Treatment of Infections. . . . . . . . . . . 154
Applications of 1M IgG Preparations for Prophylaxis of
Viral Infection ....... 156
Applications of IVIG Therapy . . . . . . . . . . . .. 160
Contents vii
Use of IVIG Preparations for Prevention and
Treatment of Specific Infection 169
Conclusion . 172
References ........... 173
9 Immunological Therapy of Endotoxaemia:
Anti-endotoxin Antibodies
A.P. Wheeler and G.R. Bernard 177
Introduction . . . . . . . . . . . 177
The Role of Endotoxin in Sepsis 177
Endotoxin: Relationship of Structure to Function 178
Approaches to Endotoxin Antagonism . . . . . 179
Mechanism of Anti-endotoxin Antibody Action . 180
The Use of Anti-core Antibodies . . . . . . . . . 180
Impact of Anti-core Antibody Class and Titre on Efficacy 181
Prospective Studies of Human Polyclonal Core
Antiserum . . . . . . . . . . . . . . . . . . . . . .. 182
Studies with Anti-core/Lipid A Monoclonal Antibodies 185
Impact of Anti-endotoxins on Cytokine Generation in
Human Sepsis. . . . . . . . . . . . . . . . . 189
Advantages and Limitations of Anti-endotoxin
Antibodies. 190
Summar;y. . 191
References 191
10 Cytokine Antibodies and Antagonists in the Treatment
of Sepsis
A.P. Wheeler and K.L. Brigham 199
Introduction . . . . . . . . . . . 199
Toxin Initiation of Sepsis . . . . 199
Properties of TNF, IL-1, IL-6 and their Receptors 200
Cytokine Interactions in Inflammation . . . . . 202
Evidence that Cytokines are Involved in Sepsis. 203
Therapeutic Strategies . 208
Summary. . 212
References 212
Index. . . . . . 225
Preface
We live in an era of unprecedented technical and scientific advance
and nowhere is this more evident than in the production and use
of antibodies for diagnostic and therapeutic purposes. Thus the
past 20 years have witnessed the use of ovine antibody fragments
for the treatment of drug overdose; the production of murine
monoclonal antibodies by means of hybridoma technology; the
exploitation of molecular biology to provide chimeric antibodies;
and the design of immunogens which result in specific antibodies
with catalytic activity.
Many scientists are expert at marketing their newest ideas
to their commercial colleagues. Every statement has the ring
of sincerity; problems are non-existent or easy to surmount;
production will cause no problems; costs can soon be markedly
curtailed; and large fortunes wait merely to be claimed. Success
remains certain until, with happy abandon, they change their minds
and move to an even more innovative and questionable approach,
leaving the investing public with massive losses and the business
executives to seek new posts. This is a particular problem in some
companies in which to question an accepted course of action
may be regarded as unacceptable pessimism, disloyalty, heresy or
worse. Many companies must even now be planning to introduce
molecular-engineered synthetic antibodies to replace their recently
discarded monoclonal products or urging an increasingly reluctant
public to invest in the distant haven of catalytic antibodies.
Several recent books and monographs have been devoted to
monoclonal and related antibodies and there is no doubt that,
in appropriate situations, they have much to offer clinically.
Furthermore, their present disadvantages (such as high cost and
frequent lack of efficacy) will be overcome eventually. While
this book covers some new topics, such as catalytic antibodies,
it is unique in focusing attention on the successful therapeutic
application of polyclonal antibodies and their fragments. Such
products, although seemingly old-fashioned, offer the advantages
of several million years' natural evolutionary development and can
be produced with a fraction of the effort and at a fraction of
the cost of their monoclonal counterparts. Another attribute
x Preface
is that such products are usually effective, in keeping with the
observation that the body invariably mounts a polyclonal humoral
immune response.
J. Landon
T. Chard
Contributors
Dr Gordon R. Bernard, Center for Lung Research, School of
Medicine, Vanderbilt University, Nashville, Tennessee 37231-
2650, USA
Dr K. L. Brigham, Division of Pulmonary Care and Critical
Medicine, Department of Medicine, Vanderbilt University,
Nashville, Tennessee 37232, USA
Professor Tim Chard, Department of Reproductive Physiology,
St Bartholomew's Hospital Medical College, West Smithfield,
London EC1A 7BE, UK
Miss Ruth E. Coxon, Department of Chemical Pathology, St
Bartholomew's Hospital Medical College, West Smithfield,
London EC1M 7BQ, UK
Dr Gerry Gallacher, Division of Chemistry, Department of
Pharmacy, University of Brighton, Cockroft Building, Lewes
Road, Moulsecoomb, Brighton BN2 4GJ, UK
Professor Frank Hay, Division of Immunology, Department of
Cellular and Molecular Sciences, St George's Hospital Medical
School, Cranmer Terrace, London SW17 ORE, UK
Dr Andrew J. Heath, 50 Otis Street, Westborough, MA 01581-
4500, USA
Dr P. A. Knight, Wellcome Biotech, Langley Court, Beckenham,
Kent BR3 3BS, UK
Professor J. Landon, Department of Chemical Pathology, St
Bartholomew's Hospital Medical College, Charterhouse Square,
London EC1M 7BQ, UK
Dr J. A. Ledermann, Department of Oncology, The Court auld
Institute of Biochemistry, 9 Ridinghouse Street, London W1P
9BT, UK
xii Contributors
Dr Charles McLean, Department of Chemical Pathology, St
Bartholomew's Hospital Medical College, Charterhouse Square,
London ECIM 7BQ, UK
Dr T. Poulton, Division of Immunology, Department of Cellular
and Molecular Sciences, St George's Hospital Medical School,
Cranmer Terrace, London SW17 ORE, UK
Dr Damon C. Smith, Therapeutic Antibodies Ltd, Department
of Chemical Pathology, St Bartholomew's Hospital Medical
College, Charterhouse Square, London ECIM 7BQ, UK
Dr R. D. G. Theakston, Liverpool School of Tropical Medicine,
Pembroke Place, Liverpool, UK
Dr A. P. Wheeler, Division of Pulmonary and Critical Care
Medicine, Department of Medicine, Vanderbilt University,
Nashville, Tennessee 37232, USA
Miss J. A. Woolley, Department of Chemical Pathology, St
Bartholomew's Hospital Medical College, Charterhouse Square,
London ECIM 7BQ, UK
Dr Peng Lee Yap, Department of Transfusion Medicine, Royal
Infirmary, Edinburgh EH3 9HB, UK