Clinical Applications of Monoclonal Antibodies

254 Pages·1988·11.85 MB·English

by  U. Zimmermann

CLINICAL
APPLICATIONS
OF MONOCLONAL
ANTIBODIES
CLINICAL
APPLICATIONS
OF MONOCLONAL
ANTIBODIES
Edited by
Ron Hubbard and Vincent Marks
University of Surrey
Guildford, Surrey, United Kingdom
SPRINGER SCIENCE+BUSINESS MEDIA, LLC
Library of Congress Cataloging in Publication Data
Clinical applications of monoclonal antibodies I edited by Ron Hubbard and Vincent
Marks.
p. cm.
Proceedings of an international symposium held Sept. 15-17, 1987, at the University
of Surrey, Guildford, U .K.
Includes bibliographies and index.
ISBN 978-1-4612-8861-9 ISBN 978-1-4613-1573-5 (eBook)
DOI 10.1007/978-1-4613-1573-5
l. Antibodies, Monoclonal-Diagnostic use-Congresses. 2. Antibodies,
Monoclonal-Therapeutic use-Congresses. I. Hubbard, Ronald. II. Marks, Vincent.
[DNLM: l. Antibodies, Monoclonal-congresses. QW 575 C6407 1987)
RB46.5.C53 1988
616'.07'56-dc19
DNLM/DLC 89-3451
for Library of Congress CIP
Proceedings of an International Symposium on the Clinical
Applications of Monoclonal Antibodies, held September 15-17, 1987,
at the University of Surrey, Guildford, United Kingdom
© 1988 Springer Science+Business Media New York
Originally published by Plenum Press, New York in 1988
All rights reserved
No part of this book may be reproduced, stored in a retrieval system, or Iransmitted
in any form or by any means, electronic, mechanical, photocopying, microfilming,
recording, or otherwise, without written permission from the Publisher
PREFACE
Immunology has come a long way in the hundred or so years since the
general concepts were first enuciated by Metchnikoff, Ehrlich, Von Bebring
and others, One of the landmarks in this progress was the invention and
development of monoclonal antibody secreting hybridomas by Milstein and bis
co-workers in Cambridge. Unlike most modern inventions of this importance
that of monoclonal antibody production was made available to the scientific
community tbroughout the world unimpeded by patent protection. This may
explain tbe unusual rapidity witb which it has been applied to the benefit
of mankind in general. This book, representing as it does the proceedings
of tbe first International Symposium to be held on the clinical appli
cations of monoclonal antibodies, shows just how much bas been achieved
within the space of little more than a decade. The enormaus promise of
monoclonal antibody technology, which became apparent soon after its
discovery, has already progressed a long way towards fulfillment. The
contributors to tbis volume, all of whom are actively engaged in monoclonal
antibody development and application, represent the state of the art.
Professor Vincent Marks
V
INTRODUCTION
It has been some twelve years since the pioneering experiments of
Köhler and Milstein led to the discovery of monoclonal antibodies. Single
molecular species antiborlies with desired specificities could be produced
by the fusion of antibody - producing cells with neoplastic cells. The
original aims of Köhler and Milstein were to study the size of the antibody
repertoire and to assess the contribution of somatic mutation to antibody
diversity. The applications of these single monoclonal antihoclies were not
completely obvious then, but it was clear they would be of significant
value.
In fact we now look back on the production of monoclonal antiborlies as
a most exciting and tremendous discovery which has led to a vast range of
applications including analytical, diagnostic and therapeutic spanning all
the chemical, biological and medical sciences.
Applications of monoclonals in research are worldwide and they have
clearly been extensively studied for use in immunoassay and immuno
purification of a wide range of industrially and clinically important
chemicals, biochemieals and microbiological materials. Clinical appli
cations also include immunocytochemistry, imaging, sensors, diagnosis and
therapy in man and in the veterinary fields.
A number of advances in the technology of the production of monoclonal
antiborlies have occurred and these are highlighted in this book. The
production of human monoclonal antiborlies in very large quantities, has
become increasingly important since they are required for human therapeutic
application. Mouse or rat monoclonals remain perfectly suitable for
analytical, diagnostic, and research applications.
We can now also look forward to a new, secend generation of monoclonal
antiborlies which involve new technologies including molecular biology. It
is now possible to modify the antibody molecule extensively, for example
(1) hybrid antiborlies have arms of different specificity thus enabling them
to be used as a bridge between two different chemical structures; (2)
chimeric antiborlies which are produced by genetic engineering allowing the
V-region mouse genes to be linked to the C-region human genes; these anti
hodies are less immunogenic in man and are much less likely to produce
side-effects in human therapy; (3) CDR (complementary determining region)
graft antiborlies have only the amino acid residues from the mouse as the
antigen-binding site i.e., the hypervariable amino acids of the V domains,
whilst the rest of the molecule can be human. Clearly with these new
antibodies come new applications and safer human therapy.
This book represents the state of the art in the research into, and
the value of, monoclonal antibodies in clinical and veterinary appli
cations. The book provides background to the development of certain topics
and highlights current areas of progress. This book will be of great
interest to research workers in the field and clinicians in general, but is
accessible to the non-specialist with an interest in these topics and hence
it has broad educational value.
We are grateful to the many eminent scientists and clinicians who
contributed to the meeting with presentations and discussions, and to the
secretariat and graduate students of the University of Surrey Biochemistry
Department who helped in a variety of roles to ensure the success of the
Symposium. In particular the editors would like to give special thanks to
Peter Goldfarb, Jan McCall and Ann Hanson for all their help.
The Symposium organisers are also most grateful to our sponsors
including Celltech Ltd., Cetus Corporation and Serono Diagnostics Ltd.
Finally the editors wish to record their thanks to the staff of Plenum
Press and Medimedia Ltd. who gave us every encouragement to realise this
project.
R. Hubbard
Department of Biochemistry
University of Surrey
July 1988
viii
CONTENTS
Introduction
Dr R. Hubbard
SECTION A
PRODUCTION AND PURIFICATION OF MONOCLONAL ANTIBODIES
The Potential of Electrofusion for Hybridoma Production
U. Zimmermann, J.J. Schmitt and P. Kleinhans 3
Production of Human Monoclonal Antihoclies using Epstein
Barr Virus
E.V. Walls, K. Lam and D.H. Crawford 21
Humanizing Recombinant Antihoclies
L. Riechmann 33
SECTION B
MONOCLONAL ANTIBODIES IN THE CLINICAL LABORATORY
Immunoassays into the 1990s
J. Landon and S. Akman 37
Methods and Labels in Immunoassay
R. Ekins 41
Monoclonal and Polyclonal Antihoclies for Immunoassay
J.S. Woodhead, J.P. Aston, R.C. Brown and I. Weeks 61
Monoclonal Antiborlies in Chemiluminescent Immunoassays
I. Weeks and J.S. Woodhead 69
Monoclonal Antihoclies to Human Estrogen and Progesterene
Receptors
G.L. Greene 81
Monoclonal Antihoclies to the Insulin Receptor
K. Siddle, M.A. Soos, R. O'Brien, R.H. Gauderton
and T.S. Pillay 87
Monoclonal Antihoclies for the Study of Human Growth Hormone
Forms and Variants
F. Frankenne, J. Closset, F. Gomez, G. Pirens, J. Smal
and G. Hennen 101
ix
SECTION C
CLINICAL AND VETERINARY APPLICATIONS OF MONOCLONAL ANTIBODIES
Monoclonal Antibodies against Rabies Virus
W.H. Wunner, B. Dietzschold, C.E. Rupprecht and H. Koprowski 115
The Diagnosis, Prevention and Treatment of Human Cytomegalovirus
Infections using Human and Murine Monoclonal Antibodies
D. Emanuel, J. Peppard, J. Chehimi, U. Hammerling
and R. O'Reilly 139
Generation and Applications of Human Monoclonal Antibodies to
Herpes Viruses
P.A. Bradshaw, S. Perkins, E.T. Lennette, J. Rowe
and S.K.H. Foung 149
Monoclonal Antibodies to Gram-negative Bacteria
C.M.M. Stern 159
Clinical Applications of Monoclonal Antibodies against
Mycobacteria
A.R.M. Coates, P. Baird, H. Nicholai and Y. Nitzan 167
Use of Monoclonal Antibodies in Malaria
J.A. Deans 179
Production and Use of Bovine and Ovine Monoclonal Antibodies
D.J. Groves and B.A. Morris 187
The Production and Uses of Monoclonal Antibody Vaccines
R.E. Spier and D. Langley 199
Antibody-targeted Plasminogen Activators
E. Haber, M.S. Runge, C. Bode, E.E. Branscomb,
J.M. Schnee, T. Quertermaus and G.R. Matsueda 207
SECTION D
ANTIBODIES IN TUMOR DIAGNOSIS AND THERAPY
Monoclonal Antibodies in the Diagnosis and Treatment of Cancer
K. Sikora 217
Anti-tumor effects of Monoclonal Antibody-ricin Conjugates
in vitro and in vivo
D.C. Blakey and P.E. Thorpe 233
Limitations in Localizing and Killing Tumors using
Radiolabelied Antibodies
A.R. Bradwell, P.W. Dykes and A.T.M. Vaughan 245
Index 253
X
SECTION A
PRODUCTION AND PURIFICATION OF MONOCLONAL ANTIBODIES