Ernst Schering Research Foundation Workshop 30 Therapeutic Vaccination Strategies

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1 Ernst Schering Research Foundation Workshop 30 Therapeutic Vaccination Strategies

2 Springer-Verlag Berlin Heidelberg GmbH

3 Ernst Schering Research Foundation Workshop 30 Therapeutic Vaccination Strategies P. Walden, W. Sterry, H. Hennekes Editors With 37 Figures and 9 Tables t Springer

4 Series Editors: G. Stock and M. Lessl ISSN ISBN CIP data applied for Die Deutsche Bibliothek - CIP-Einheitsaufnahme Schering-Forschungsgesellschaft <Berlin>: Emst Schering Research Foundation Workshop. ISSN Therapeutic Vaccination Strategies Therapeutic Vaccination Strategies ; with tables / P. Walden. W. Sterry, H. Hennekes, ed. (Emst Schering Research Foundation Workshop; 30) ISBN ISBN (ebook) DOI / This work is subject to copyright. AII rights are reserved, whether the whole or part of the material is concemed, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction an microfilms or in any other way, and storage in data banks. Duplication of this publication or parts thereof is permitted only under the provisions of the German Copyright Law of September 9, 1965, in its CUITent version, and permission for use must always be obtained from Springer-Verlag Berlin Heidelberg GmbH Violations are liable for prosecution under the German Copyright Law. Springer-Verlag Berlin Heidelberg 2000 Originally published by Springer-Verlag Berlin Heidelberg New York in 2000 Softcover reprint of the hardcover 1 st edition 2000 The use of general descriptive names, registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Product liability: The publishers cannot guarantee the accuracy of any information about dosage and application contained in this book. In every individual case the user must check such information by consulting the relevant literature. Typesetting: Data conversion by Springer-Verlag SPIN: l/3 I 34/AG I 0- Printed on acid-free paper

5 Preface The induction of immune responses against tumor cells by vaccination is rapidly evolving as a therapeutic modality with new potentials for the treatment of cancer. It is based on the fact that our immune system can identify tumor cells and, once activated, is capable of developing specific immunity against the neoplastic cells. Numerous observations and intense research clearly document the major contribution of the immune system to the prevention of cancer. And there are many reports of patients suffering from malignant melanoma or other tumors who mount a spontaneous immune response against their tumor cells that results in tumor regression. Based on the recent advances in our understanding of the components of our immune system, their interactions and the regulation of immune responses, we are now able to design vaccination strategies that induce or enhance cell-mediated immunity against tumors. A major advancement came with the identification and characterization of relevant tumor antigens, which are suitable target structures for anti-tumor immune response. First clinical trials using such vaccine strategies have yielded encouraging results in patients. However, in spite of many reported cases of successful therapy of cancer by vaccination many patients still do not experience relief after such treatments. These initial clinical trials and the accompanying investigations have revealed a number of important results that indicate the direction of future research and development in the field. With a two-day workshop held in May 1999 in Berlin, Germany, we attempted to join experts from different fields related to therapeutic vaccination in order to evaluate the current status and to discuss the fu-

6 VI Preface The participants of the workshop ture directions of the development of strategies for cancer immune therapy. The topics explored included the basic principles of anti-cancer immunity and of successful vaccination therapy, such as the identification of suitable tumor antigens, adjuvants, or vectors. Recurring themes were the need for and the utilization of immune monitoring techniques which are required for the evaluation of the vaccination effects and as basis for a systematic development of new therapeutic approaches, as well as the clinical criteria for the selection of cancers that are suitable for immune therapy and the clinical settings required. The workshop was organized in four sessions covering the basic concepts, the available technologies, the clinical conditions for and experiences with therapeutic vaccination trials, and the legal considerations for their clinical application. Extending the scope of the workshop, new concepts for the use of vaccination strategies for the elimination or attenuation of autoreactive T cells in autoimmune diseases were discussed as well.

7 Preface VII We are indebted to the Ernst Schering Research Foundation for providing us with the necessary resources for this workshop and the support of the representatives of the Foundation in the organization of this meeting. We wish to thank the speakers and the participants for their most valuable presentations and lively discussions at the workshop and the authors of the chapters in this proceedings volume for their contributions. We also thank the chairpersons, Drs. Dominik Mumberg, Ruth Thieroff-Ekerdt, and Michael Topert of Schering AG, Berlin, Germany, and Dr. David Henderson of Berlex Biosciences, Richmond, Calif., USA, for guiding the sessions. Peter Walden, Wolfram Sterry, Hartwig Hennekes

8 Table of Contents Vaccination Therapy for Malignant Disease: The Clinical Perspective W. Sterry Tumor Antigens P. Walden... Costimulatory Molecules in Vaccine Design J. Hodge, J. Schlom Application oft Cell Immunotherapy for Human Viral and Malignant Diseases S.R. Riddell, E.H. Warren, D. Lewinsohn, H. Mutimer, M. Topp, L. Cooper, R. de Fries, P.D. Greenberg 53 5 Immune Monitoring in Cancer Immunotherapy P. Romero, M.J. Pittet, D. Valmori, D.E. Speiser, V. Cerundolo, D. Lienard, F. Lejeune, f.-c. Cerottini 75 6 Retroviral Vectors for Cancer Gene Therapy M. Collins CpG Oligonucleotides as Immune Adjuvants A. Krieg

9 X Table of Contents 8 DNA Vaccination Against Cancer Antigens F.K. Stevenson, D. Zhu, M.B. Spellerberg, J. Rice, CA. King, A.R. Thompsett, S.S. Sahota, T.J. Hamblin Skin Cancer- Prospects for Novel Therapeutic Approaches G. Sting! The Hybrid Cell Vaccination Approach to Cancer Immunotherapy U. Trefzer, G. Herberth, W. Sterry, P. Walden T Cell Receptor Peptides for the Vaccination Therapy of Multiple Sclerosis S. Brocke Regulatory Aspects of Cancer Gene Therapy and DNA Vaccination K. Cichutek Subject Index.. Previous Volumes Published in this Series

10 List of Editors and Contributors Editors H. Hennekes Schering AG, Experimental Dermatology, Mtillerstrasse 178, Berlin, Germany W. Sterry Department of Dermatology and Allergy, Medical Faculty Charite, Humboldt University, Schumannstrasse 20/21, Berlin, Germany P. Walden Department of Dermatology and Allergy, Medical Faculty Charite, Humboldt University, Schumannstrasse 20/21, Berlin, Germany Contributors S. Brocke Hebrew University Jerusalem, Hadassah Medical School, Department of Pathology, P.O. Box 12272, Jerusalem, Israel J. -C. Cerottini Division of Clinical Onco-Immunology, Ludwig Institute for Cancer Research Lausanne Branch, University of Lausanne, Lausanne, Switzerland V. Cerundolo Molecular Immunology Group, Nuffield Department of Medicine, John Radcliffe Hospital, Oxford, UK

11 XII List of Editors and Contributors K. Cichutek Paul-Ehrlich-Institut, Bundesamt fi.ir Sera und Impfstoffe, Abteilung Medizinische Biotechnologie, Paul-Ehrlich-Strasse 51-59, Langen, Germany M. Collins Department of Immunology, Windeyer Institute of Medical Sciences, 46.Cleveland Street, London WlP 6DB, UK L. Cooper R. de Fries P.D. Greenberg T.J. Hamblin G. Herberth Department of Dermatology and Allergy, Medical Faculty Charite, Humboldt University, Schumannstrasse 20/21, Berlin, Germany J.W. Hodge National Cancer Institute, Tumor Immunology and Biology Branch, National Institute of Health, Building 10, Room 5B38, Bethesda, MD 20879, USA C.A. King A.M. Krieg University of Iowa, Department of Internal Medicine, 540 EMRB, Iowa City, IA 52242, USA

12 List of Editors and Contributors XIII F. Lejeune Multidisciplinary Oncology Center, University Hospital, Lausanne, Switzerland D. Lewinsohn D. Liinard Division of Clinical Onco-lmmunology, Ludwig Institute for Cancer Research Lausanne Branch, University of Lausanne, Lausanne, Switzerland H. Mutimer M.J. Pittet Division of Clinical Onco-Immunology, Ludwig Institute for Cancer Research Lausanne Branch, University of Lausanne, Lausanne, Switzerland J. Rice S.R. Riddell P. Romero Division of Clinical Onco-Immunology, Ludwig Institute for Cancer Research Lausanne Branch, University of Lausanne, Lausanne, Switzerland S.S. Sahota J. Schlom National Cancer Institute, Tumor Immunology and Biology Branch, National Institute of Health, Building 10, Room 5B38, Bethesda, MD 20879, USA

13 XIV List of Editors and Contributors D.E. Speiser Division of Clinical Onco-Immunology, Ludwig Institute for Cancer Research Lausanne Branch, University of Lausanne, Lausanne, Switzerland M.B. Spellerberg W. Sterry Department of Dermatology and Allergy, Medical Faculty Charite, Humboldt University, Schumannstrasse 20/21, Berlin, Germany F. K. Stevenson G. Stingl Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology, Wlihringer Giirtell8-20, 1090 Vienna, Austria A.R. Thompsett M. Topp U. Trefzer Department of Dermatology and Allergy, Medical Faculty Charite, Humboldt University, Schumannstr. 20/21, Berlin, Germany D. Valmori Division of Clinical Onco-Immunology, Ludwig Institute for Cancer Research Lausanne Branch, University of Lausanne, Lausanne, Switzerland P. Walden Department of Dermatology and Allergy, Medical Faculty Charite, Humboldt University, Schumannstrasse 20/21, Berlin, Germany

14 List of Editors and Contributors XV E.H. Warren D.Zhu