Vaccine Intervention Against Virus-Induced Tumours

114 Pages·1986·12.958 MB·English

by  J. M. Goldman, M. A. Epstein (eds.)

Vaccine Intervention Against Virus-induced Tumours
LEUKAEMIA AND LYMPHOMA RESEARCH
Vaccine Intervention against
Virus-induced Tumours
Edited by
J. M. Goldman
Consultant Physician
Royal Postgraduate Medical School
Hammersmith Hospital
London W12 OHS, UK
and
M. A. Epstein
Professor of Pathology
University of Bristol Medical School
Bristol BS8 lTD, UK
M
MACMILLAN
© The Leukaemia Research Fund 1986
Softcover reprint of the hardcover 1st edition 1986 978-0-333-39830-2
All rights reserved. No reproduction, copy or transmission
of this publication may be made without written permission.
No paragraph of this publication may be reproduced, copied
or transmitted save with written permission or in accordance
with the provisions of the Copyright Act 1956 (as amended).
Any person who does any unauthorised act in relation to
this publication may be liable to criminal prosecution and
civil claims for damages.
First published 1986
Published in Great Britain by
THE MACMILLAN PRESS LTD
Houndmills, Basingstoke, Hampshire RG21 2XS
and Lond~n
Companies and representatives
throughout the world
British Library Cataloguing in Publication Data
Vaccine intervention against virus-induced
tumours.-(Leukaemia and lymphoma research)
1. Viral carcinogenesis 2. Tumors-
Preventive inoculation
I. Goldman, John M. II. Epstein, M. A. III. Series
614.5'999 RC268.57
ISBN 978-1-349-08245-2 ISBN 978-1-349-08243-8 (eBook)
DOI 10.1007/978-1-349-08243-8
Contents
The Contributors vi
Preface vii
The Leukaemia Research Fund xi
1. Hepatitis B Virus and Primary Cancer of the Liver
Baruch S. Blumberg
2. Vaccination against Marek's Disease
L. J. N. Ross and P. M Biggs 13
3. Studies on the Prevention ofEBV-induced Malignancies by a
Subunit Antiviral Vaccine
M. A. Epstein 33
4. Prevention of Primary Liver Cancer by Hepatitis B Vaccines
Arie J. Zuckerman 47
5. Human Papillomavirus Infections and Prospects for Vaccination
Harald zur Hausen 63
6. Vaccine Strategies against the Human Retroviruses Associated
with AIDS
Robert C. Gallo, Peter J. Fischinger and Dani P. Bolognesi 81
7. The Role of Cytomegalovirus in Kaposi's Sarcoma and Acquired
Immune Deficiency Syndrome
Gaetano Giraldo and Elke Beth-Giraldo 93
Index 105
The Contributors
E. Beth-Giraldo R. C. Gallo
Division of Viral Oncology Building 37, Rm 6A09
Pascale Institute NIH, National Cancer Institute
80131 Naples Bethesda, Maryland 20205
Italy USA
P.M. Biggs G. Giraldo
Houghton Poultry Research Station Division of Viral Oncology
Houghton, Huntingdon Pascale Institute
Cambs PEl 7 2DA 80131 Naples
UK Italy
B. S. Blumberg H. zur Hausen
Institute for Cancer Research Cancer Research Centre
7701 Burholme Avenue, Fox Chase Im Neuenheimer Feld 280
Philadelphia, PA 19111 D-6900 Heidelberg l
USA West Germany
D. P. Bolognesi L. J. N. Ross
Building 37, Rm 6A09 Houghton Poultry Research Station
NIH, National Cancer Institute Houghton, Huntingdon
Bethesda, Maryland 20205 Cambs PE17 2DA
USA UK
M. A. Epstein A. J. Zuckerman
Department of Pathology Department of Medical Microbiology
University of Bristol Medical School London School of Hygiene and Tropical Medicine
Bristol BS8 1T D Keppel Street
UK London WClE 7HT
P. J. Fischinger
Building 37, Rm 6A09
NIH, National Cancer Institute
Bethesda, Maryland 20205
USA
Preface
This volume is the third in the series entitled Leukaemia and Lymphoma Research,
which was initiated in 1984. The Annual Guest Lecture, around which the volume
was constructed, was delivered by Professor M. A. Epstein, and reviewed his
work culminating in the development of a vaccine that can prevent virus-induced
lymphomas in tamarin monkeys. Thus he and the other contributors to this
volume describe, in varying degrees of detail, the progress of efforts to prevent
selected malignant diseases in man and animals by use of purpose-made vaccines.
To the newcomer, the surprise might be not so much that viruses can cause
(or be co-factors in causing) leukaemias, lymphomas and solid tumours in man,
but that it took so long for the general principle to be acknowledged by the
scientific community. The history is long enough. Viruses, of course, are a
comparatively recent concept, but filterable agents (ill-defined agents smaller
than the smallest known bacteria that could traverse asbestos filter pads or
unglazed porcelain filter candles) were known since the end of the last century.
In 1908 Ellermann and Bang in Copenhagen succeeded in transmitting erythro
myeloblastic leukaemia in chickens by transfer of mterable material from
affected birds; three years later, Peyton Rous at the Rockefeller Institute in New
York, transmitted the first solid tumour (a sarcoma) from diseased chickens to
normal recipients. (He received a Nobel prize for this work only in 1965 .)
There then followed a long interval during which there were no further
reports of leukaemia or solid tumours transmitted by filterable agents. In the
early 1930s, however, Richard Shope in New Jersey reported the transmission of
rabbit fibroma by filtrates, and subsequently transmission of rabbit papillomas.
In 1936 John Bittner at Bar Harbor reported that an agent capable of causing
mouse mammary carcinoma could be transmitted through the milk of nursing
female mice. Two years later Baldwin Lucke in Philadelphia provided evidence
that a kidney carcinoma of frogs was caused by a transmissible virus.
In the 1950s much evidence accumulated linking various RNA-containing
viruses with tumours and leukaemias in rodents. Ludwig Gross reported in 1951
that filtrates from 'infected' animals could transmit leukaemia in mice, and in
X PREFACE
1957 Stewart and Eddy at the National Cancer Institute defined an agent (a
polyoma virus) capable of causing parotid tumours in new-born mice. In 1957,
Charlotte Friend at the Sloan Kettering Institute in New York, isolated a filter
able agent that could induce an erythroblastosis-like syndrome in weanling mice.
In 1960 Eddy and Girardi separately reported that a simian virus (SV40) could
cause sarcomas in new-born hamsters. In 1962 John Trentin showed that an
adenovirus could also induce sarcomas in hamsters. In 1964 William Jarrett
reported the transmission by a virus of leukaemia/lymphoma in cats. This is a
very incomplete catalogue of the landmarks of the first fifty-odd years of viral
oncology, but it serves to illustrate how spasmodic was the progress. Initially
the concept that viruses could cause malignant disease was discounted by almost
all; subsequently many accepted that viruses could, in isolated or experimental
situations, cause tumours in animals, but they believed that the examples were
irrelevant to man.
Much has now changed over the last 20 years. Perhaps the new era dawned
with the demonstration in 1964 of a new herpes-like virus (now named EBV)
associated with characteristic lymphoma described originally by Denis Burkitt in
East African children. Though rigorous proof that this agent causes Burkitt's
lymphoma is not yet available, the circumstantial evidence in favour is com
pelling. In the 1970s, one of the causative agents of infectious hepatitis (the
hepatitis B virus) was identified and this now seems to be a major co-factor in
the aetiology of hepatocarcinoma in many parts of the world, perhaps less so in
Europe and North America. One of the later pieces of the jigsaw is the recog
nition of a distinctive RNA virus, termed ATV or HTLV-1, as a probable cause
of adult T-cell leukaemia lymphoma in Japan and the Caribbean. Though one
must immediately concede that the evidence linking viruses with the bulk of
common human tumours is weak or non-existent, it is now clear nonetheless
that some tumours would almost certainly not have occurred if a specific co
factor, in this case the virus, were deleted from the environment or at least
eradicated from the body.
This then is the background for attempts to immunise susceptible humans
against the potentialleukaemogenic or carcinogenic effects of different viruses.
To my knowledge this is the first attempt to assemble under one cover details
of the various vaccinal approaches to the prevention of human and animal
tumors. I hope the reader will find this volume informative and to some
extent also entertaining. I hope it points the way to important therapeutic
advances in the future.
I thank all the authors for their contributions. They were all delivered before
or very soon after the specified date. Editors are always very grateful when the
targets are achieved by all.
London, April1986 J.M.G.
M.A. E.
The Leukaemia Research Fund
The Leukaemia Research Fund is the only national charitable foundation in
Britain devoting all its resources to research and patient care in leukaemia and
the related blood diseases. Founded in 1960, it is the third largest cancer organ
isation in Britain and is a member of the United Kingdom Co-ordinating
Committee on Cancer Research. The Fund is advised by a distinguished Medical
and Scientific Advisory Panel.
The Fund finances an expanding programme of research and has recently set
up the Leukaemia Research Fund Centre at the Institute of Cancer Research in
London for the study of the molecular and cellular biology of human leukaemia.
It has also introduced a large-scale progressive aetiology study in Britain with
particular emphasis on the biology of the diseases, and has funded pioneering
work in Britain on bone-marrow transplantation. In addition, the Fund is
involved in the clinical support of patients and provides a full information
service. Its academic work, including international symposia, workshops and
lectures, is complemented by an active policy of world-wide collaboration. The
Leukaemia Research Fund Annual Guest Lecture is delivered by a scientist or
doctor who has made a major contribution to knowledge of leukaemia and
lymphomas.
1 Baruch S. Blumberg
Hepatitis B Virus and Primary Cancer
of the Liver
Introduction
In this introductory chapter the use of vaccines to intervene against virus-induced
tumours will be discussed, the hepatitis B virus (HBV) and its causative role in
primary hepatocellular carcinoma (PHC) being used as an example.
The vaccine which is currently in use will be discussed first. There will follow
a summary of the evidence supporting the hypothesis that HBV is the cause of
PHC. (This topic will be discussed in greater detail in Chapter 4 in this volume.)
The consequence of accepting this hypothesis will then be considered. There are
unusual features of the HBV-PHC relation which are not explained by current
viral cancer models. A model introduced by London and Blumberg1'2 to explain
these relations will be presented. The model is of heuristic value, in that it suggests
interesting experiments and novel approaches to diagnosis and therapy which
may have application to other virus-caused cancers. A broad description of the
public health and clinical programmes in progress and planned will then be given.
Each time a medical solution is introduced, it raises other problems, many of
which were not anticipated. The prevent}on of HBV infection is no exception.
As an example of such a problem, the possible role of HBV in the determination
of the sex of the offspring of infected parents and how this may be affected by
vaccination programmes will be briefly reviewed. This interesting biological and
medical phenomenon may also occur with other viruses.
Vaccines
Evidence has been accumulating since the early 1970s3•4 supporting the
hypothesis that persistent infection with HBV is required for the development of
the disease: that is, that HBV is a necessary cause ofPHC. There is now substan
tial support for this hypothesis. Massive public health programmes are in place or
planned, to prevent infection with HBV and thereby, presumably, prevent primary
cancer of the liver as well as acute and chronic liver disease due to HBV, which