Systemic Radiotherapy with Monoclonal Antibodies: Options and Problems

199 Pages·1996·3.96 MB·English

by  S. Matzku (auth.)

Recent Results 141
in Cancer Research
Managing Editors
Ch. Herfarth, Heidelberg· H.-f. Senn, St. Gallen
Associate Editors
M. Baum, London· V. Diehl, K6ln
F. Gutzwiller, Zurich· M.F. Rajewsky, Essen
M. Wannenmacher, Heidelberg
Founding Editor
P. Rentchnik. Geneva
Springer
Berlin
Heidelberg
New York
Barcelona
Budapest
Hong Kong
London
Milan
Paris
Santa Clara
Singapore
Tokyo
M.-L. Sautter-Bihl H. Bihl
M. Wannenmacher
(Eds.)
Systemic
Radiotherapy
with Monoclonal
Antibodies
Options and Problems
With 56 Figures and 20 Tables
i
Springer
Priv.-Doz. Dr. Marie-Luise Sautter-Bihl
Arztliche Direcktorin der
Klinik fUr Strahlentherapie
Stadt. Kliniken Karlsruhe
MoltkestraBe 14-16
76133 Karlsruhe, Germany
Priv.-Doz. Dr. Dr. Heiner Bihl
Klinik fur Nuklearmedizin
Katharinenhospital Stuttgart
Kriegsbergstr. 60
70174 Stuttgart, Germany
Professor Dr. Dr. Michael Wannenmacher
Radiologische Klinik
Abteilung fUr Klinische Radiologie
1m Neuenheimer Feld 400
69120 Heidelberg, Germany
ISBN-13:978-3-642-79954-9 e-ISBN-13:978-3-642-79952-5
DOl: 10.1007/978-3-642-79952-5
Library of Congress Cataloging-in· Publication Data. Systemic radiotherapy with
monoclonal antibodies: options and problems/H. Bihl, M. Wannenmacher, (eds.).
p. cm. - (Recent results in cancer research; 141) Includes bibliographical refer
ences and index.lSBN-13:978-3-642-79954-9 (hardcover)1.Cancer-Radioimmuno·
therapy. 2. Monoclonal antibodies-Therapeutic use. I. Bih\' H. (Heiner) II.
Wannenmacher, M. (Michael) III. Series. [DNLM: 1. Neoplasms-radiotherapy.
2. Radioimmunotherapy-methods. 3. Antibodies, Monoclonal-therapeutic use.
WI RE106P v.141 1996/QZ 269 S995 1996] RC261.R35 no. 141 [RC271.R26]
616.99'4 s-dc20 [616.99'40642] DNLMIDLC for Library of Congress 96-41925
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Preface
Almost a century ago Paul Ehrlich introduced the "magic
bullet" concept of targeting therapeutic agents to specific
tissues in order to reduce systemic toxicity. Due to the
advances in hybridoma technology in the 1980s, monoclonal
antibodies (MAbs) with their exquisite affinity to tumor
antigens have become powerful tools in the treatment of
cancer, especially when linked to therapeutic agents such as
radionuclides, drugs, toxins, or enzymes. It can now be
expected that such agents will lead to new cancer treatments
with high therapeutic success rates.
However, there are major problems in developing this
therapeutic concept to a routine treatment modality. This is
partly due to factors such as heterogenous distribution of
tumor antigens, insufficient blood supply of tumors, high
interstitial pressure, and the large interstitial space that
antibodies have to traverse. This book is focused on the
development in radio immunotherapy (RIT) using radio
labeled monoclonal antibodies as tumoritoxic agents. This
area of research has attracted the interest of clinicians and
scientists from many different disciplines. It is now clear
that the full potential of RIT can only be realized through
the concerted efforts of laboratory scientists (molecular
biologists, cell physiologists, chemists, radiation physicists,
and biologists) and cancer clinicians in nuclear medicine,
radiooncology, and internal oncology.
Although it will not be possible to cover all the areas of
the current activities in RIT research in this one volume, we
hope our selection of topics will give a taste of the exciting
possibilities this new cancer therapy can provide. The
purpose of this book is to provide a general overview of the
VI Preface
various aspects of radio labeled monoclonal antibodies in
cancer therapy, including basic problems and clinical use.
Most likely, RIT will not be a solitary therapeutic modality,
but may be a useful complement to the other established
strategies, such as surgery and chemotherapy.
The editors gratefully acknowledge the efforts of all the
contributors, many of whom have presented previously
unpublished results.
Marie-Luise Sautter-Bihl
Heiner Bihl
Michael Wannenmacher
Contents
S. Matzku
Monoclonal Antibodies in Tumor Therapy . . . . . . . . . 1
D.J. Buchsbaum and P.L. Roberson
Experimental Radioimmunotherapy:
Biological Effectiveness and Comparison
with External Beam Radiation ................... 9
F. Buchegger, l.-P. Mach, S. Folli, B. Delaloye,
A. Bischof-Delaloye, and A. Pelegrin
Higher Efficiency of l3lI-Labeled Anti
Carcinoembryonic Antigen-Monoclonal Antibody
(Fab')z as Compared to Intact Antibodies in
Radioimmunotherapy of Established Human Colon
Carcinoma Grafted in Nude Mice. . . . . . . . . . . . . . . . . 19
l.L. Humm
Problems and Advances in the Dosimetry
of Radionuclide Targeted Therapy . . . . . . . . . . . . . . . . 37
M.-L. Sautter-Bihl, G. Herbold, and H. Bihl
Minimal Residual Disease: a Target
for Radioimmunotherapy
with l3lI-Labeled Monocloncal Antibodies?
Some Dosimetric Considerations 67
l.A. 0'D onoghue
Optimal Therapeutic Strategies
for Radioimmunotherapy . . . . . . . . . . . . . . . . . . . . . . . . 77
VIII Contents
M.R. Zalutsky, J.M. Schuster, P.K. Garg,
G.E. Archer, Jr., M. W. Dewhirst, and D.D. Bigner
Two Approaches
for Enhancing Radioimmunotherapy:
Emitters and Hyperthermia. . . . . . . . . . . . . . . . . . . . 101
IX
M.-L. Sautter-Bihl and H. Bihl
Can Preirradiation Enhance Tumor Uptake of
Radiolabeled Pharmaceuticals? Experimental Data
in a Mouse Neuroblastoma Xenograft System 123
v. K. Langmuir
The Use of Radioimmunotherapy
in Combination with Bioreductive Agents ......... . 137
J. T. Kemshead, K.I. Hopkins, and c.L. Chandler
Treatment of Diffuse Leptomeningeal Malignancy
by Intrathecal Injection
o f 1311 -R a d·1 0.1 mmunocon.J ugates ................. . 145
K. Hopkins, V. Papanastassiou, and J. T. Kemshead
The Treatment of Patients
with Recurrent Malignant Gliomas
with Intratumoral Radioimmunocon j ugates 159
J.F. Eary and O. W. Press
High Dose Radioimmunotherapy
in Malignant Lymphoma ........................ 177
C. T. Miyamoto, L. W. Brady, M.A. Rackover,
J. Emrich, R. Class, H. Bender, B. Micaily,
and Z. Steplewski
The Use of Epidermal Growth Factor Receptor-425
Monoclonal Antibodies Radiolabeled
with lodine-125 in the Adjuvant Treatment
of Patients with High Grade Gliomas of the Brain. . . 183
Subject Index. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193
List of Contributors*
Archer, G.E., lr. 1011 Humm,l.L. 37
Bender, H. 183 Kemshead,l.T. 145, 159
Bigner, D.D. 101 Langmuir, V.K. 137
Bihl, H. 67, 123 Mach,l.-P. 19
Bischof-Delaloye, A. 19 Matzku, S. 1
Brady, L.W. 183 Micaily, B. 183
Buchegger, F. 19 Miyamoto, C.T. 183
Buchsbaum, D.l. 9 O'Donoghue,l.A. 77
Chandler, c.L. 145 Papanastassiou, V. 159
Class, R. 183 Pelegrin, A. 19
Delaloye, B. 19 Press,O.W. 177
Dewhirst, M.W. 101 Rackover, M.A. 183
Eary,l.F. 177 Roberson, P.L. 9
Emrich,l. 183 Sautter-Bihl, M.-L. 67, 123
FoIIi, S. 19 Schuster,l.M. 101
Garg, P.K. 101 Stepleswki, Z. 183
Herbold, G. 67 Zalutsky, M.R. 101
Hopkins, K.I. 145, 159
* The address of the principal author is given on the first page of each
contribution.
I Page on which contribution begins.
Monoclonal Antibodies in Tumor Therapy
S. Matzku
E. Merck KGaA, Pharma Preclinical Research, Frankfurterstr 250,64271
Darmstadt, Germany
Introduction
It is now almost two decades since the basis of hybridoma technology was
established and it has subsequently been rapidly applied to problems of
tumor biology. It is just a decade since gene technology manipulations
(Jones et al. 1986) were successfully applied to antibodies, and the expan
sion of this approach has led to a number of fundamental modifications of
the antibody molecule (Winter and Harris 1993). With this background, it is
legitimate to consider what the bottom line of therapeutic success is and to
examine new perspectives.
The Potential of Monoclonal Antibodies
Specificity
There is a consensus that target antigens in general are essentially normal
structures which are expressed in higher density, in an overt fashion, and in
an atypical tissular context on tumor cells. Exquisite specificities have
nevertheless been identified as idiotypic determinants on B lymphoma cells,
but these had only limited impact on therapeutic approaches.
Inherent Functions
"Naked" antibody is endowed with cyctolytic capacity, one effector function
being antibody-dependent cellular cytotoxicity, the other, complement
mediated cytotoxicity. Both mechanisms rely on the IgG 1 and IgG3 isotype
(human antibodies), although clustering of antigen seems to be a major
determinant in the complement situation. A further mechanism is receptor
Recent Results in Cancer Research, Vol. 141
© Springer-Verlag Berlin· Heidelberg 1996