M E T H O D S I N M O L E C U L A R M E D I C I N ETM AAddooppttiivvee IImmmmuunnootthheerraappyy MMeetthhooddss aanndd PPrroottooccoollss EEddiitteedd bbyy BBuurrkkhhaarrdd LLuuddeewwiigg MMaatttthhiiaass WW.. HHooffffmmaannnn Adoptive Immunotherapy M E T H O D S I N M O L E C U L A R M E D I C I N ETM 111133.Multiple Myeloma: Methods and Protocols, 9966. Hepatitis B and D Protocols: Volume 2, edited by Ross D. Brown and P. Joy Ho, Immunology, Model Systems, and Clinical 2005 Studies, edited by Robert K. Hamatake and Johnson Y. N. Lau, 2004 111122.Molecular Cardiology: Methods and Protocols, edited by Zhongjie Sun, 2005 9955. Hepatitis B and D Protocols: Volume 1, Detection, Genotypes, and 111111.Chemosensitivity: Volume 2, In Vivo Characterization, edited by Robert K. Models, Imaging, and Molecular Regulators, Hamatake and Johnson Y. N. Lau, 2004 edited by Rosalyn D. Blumethal, 2005 9944. Molecular Diagnosis of Infectious 111100.Chemosensitivity: Volume 1, In Vitro Diseases, Second Edition, edited by Jochen Assays, edited by Rosalyn D. Blumethal, Decker and Udo Reischl, 2004 2005 9933. Anticoagulants, Antiplatelets, and 110099.Adoptive Immunotherapy, Methods and Thrombolytics, edited by Shaker A. Protocols, edited by Burkhard Ludewig and Mousa, 2004 Matthias W. Hoffmann, 2005 9922. Molecular Diagnosis of Genetic Diseases, 110088.Hypertension, Methods and Protocols, Second Edition, edited by Rob Elles and edited by Jérôme P. Fennell and Andrew H. Roger Mountford, 2004 Baker, 2005 9911. Pediatric Hematology: Methods and 110077.Human Cell Culture Protocols, Second Protocols, edited by Nicholas J. Goulden Edition, edited by Joanna Picot, 2005 and Colin G. Steward, 2003 110066.Antisense Therapeutics, Second Edition, 9900. Suicide Gene Therapy: Methods and edited by M. Ian Phillips, 2005 Reviews, edited by Caroline J. Springer, 2004 110055.Developmental Hematopoiesis: Methods 8899. The Blood–Brain Barrier: Biology and and Protocols, edited by Margaret H. Research Protocols, edited by Sukriti Nag, Baron, 2005 2003 110044.Stroke Genomics: Methods and Reviews, 8888. Cancer Cell Culture: Methods and edited by Simon J. Read and David Virley, Protocols, edited by Simon P. Langdon, 2003 2005 8877. Vaccine Protocols, Second Edition, edited 110033.Pancreatic Cancer: Methods and Protocols, by Andrew Robinson, Michael J. Hudson, edited by Gloria H. Su, 2005 and Martin P. Cranage, 2003 110022.Autoimmunity: Methods and Protocols, 8866. Renal Disease: Techniques and Protocols, edited by Andras Perl, 2004 edited by Michael S. Goligorsky, 2003 110011.Cartilage and Osteoarthritis: Volume 2, 8855. Novel Anticancer Drug Protocols, edited Structure and In Vivo Analysis, edited by by John K. Buolamwini and Alex A. Adjei, Frederic De Ceuninck, Massimo Sabatini, 2003 and Philippe Pastoureau, 2004 8844. Opioid Research: Methods and Protocols, 110000.Cartilage and Osteoarthritis: Volume 1, edited by Zhizhong Z. Pan, 2003 Cellular and Molecular Tools, edited by 8833. Diabetes Mellitus: Methods and Protocols, Massimo Sabatini, Philippe Pastoureau, edited by Sabire Özcan, 2003 and Frederic De Ceuninck, 2004 8822. Hemoglobin Disorders: Molecular 9999. Pain Research: Methods and Protocols, Methods and Protocols, edited by Ronald edited by David Z. Luo, 2004 L. Nagel, 2003 9988. Tumor Necrosis Factor: Methods and 8811. Prostate Cancer Methods and Protocols, Protocols, edited by Angelo Corti and edited by Pamela J. Russell, Paul Jackson, Pietro Ghezzi, 2004 and Elizabeth A. Kingsley, 2003 9977. Molecular Diagnosis of Cancer: Methods 8800. Bone Research Protocols, edited by Miep and Protocols, Second Edition, edited by H. Helfrich and Stuart H. Ralston, 2003 Joseph E. Roulston and John M. S. Bartlett, 7799. Drugs of Abuse: Neurological Reviews and 2004 Protocols, edited by John Q. Wang, 2003 M E T H O D S I N M O L E C U L A R M E D I C I N E™ Adoptive Immunotherapy Methods and Protocols Edited by Burkhard Ludewig Research Department, Kantonsspital St. Gallen, Switzerland and Matthias W. Hoffmann Department of Abdominal and Transplant Surgery, Hannover Medical School, Hannover, Germany © 2005 Humana Press Inc. 999 Riverview Drive, Suite 208 Totowa, New Jersey 07512 www.humanapress.com All rights reserved. No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise without written permis- sion from the Publisher. Methods in Molecular Medicine™ is a trademark of The Humana Press Inc. All papers, comments, opinions, conclusions, or recommendations are those of the author(s), and do not necessarily reflect the views of the publisher. This publication is printed on acid-free paper. ∞ ANSI Z39.48-1984 (American Standards Institute) Permanence of Paper for Printed Library Materials. Production Editor: Tracy Catanese Cover design by Patricia F. Cleary Cover illustration: Figure 1 from Chapter 3, “Delivery of Tumor Antigens to Dendritic Cells Using Biode- gradable Microspheres,” by Ying Waeckerle-Men, Bruno Gander, and Marcus Groettrup. Schematic representation of the regulation of dendritic cell persistence within secondary lymphoid organs by effector T-cells. Immune responses are positively regulated by dendritic cells mediating antigen influx into secondary lymphoid organs from peripheral sites such as tumor tissues. Photocopy Authorization Policy: Authorization to photocopy items for internal or personal use, or the internal or personal use of specific clients, is granted by Humana Press Inc., provided that the base fee of US $25.00 per copy is paid directly to the Copyright Clearance Center at 222 Rosewood Drive, Danvers, MA 01923. For those organizations that have been granted a photocopy license from the CCC, a separate system of payment has been arranged and is acceptable to Humana Press Inc. The fee code for users of the Transactional Reporting Service is: [0-58829- 406-4/05 $25.00]. Printed in the United States of America. 10 9 8 7 6 5 4 3 2 1 e-ISBN: 1-59259-862-5 ISSN: 1543-1894 Library of Congress Cataloging-in-Publication Data Adoptive immunotherapy : methods and protocols / edited by Burkhard Ludewig and Matthias W. Hoffmann. p. ; cm. -- (Methods in molecular medicine ; 109) Includes bibliographical references and index. ISBN 1-58829-406-4 (alk. paper) 1. Cancer--Immunotherapy. 2. Cellular therapy. 3. Immunocompetent cells--Therapeutic use. [DNLM: 1. Immunotherapy, Adoptive--methods. 2. Antibodies--therapeutic use. 3. Cytotoxicity, Immunologic. 4. Dendritic Cells. 5. Stem Cell Transplantation. 6. T-Lymphocytes. QW 940 A239 2005] I. Ludewig, Burkhard. II. Hoffmann, Matthias W. III. Series. RC271.I45A335 2005 616.99'4061--dc22 2004010540 Preface Over the last decade, the advances in cellular and molecular immunology have been tremendous. Our continuously improving understanding of the immune system and the appreciation of the mechanisms by which tumors and viral or bacterial infections are controlled have led to promising new treatment strate- gies. Adoptive transfer of tailored antigen-specific immune cells and/or opti- mally designed immunological effector molecules is an elegant and promising approach to the establishment or restoration of protective immune responses. At this point, it appears timely to publish the present volume on Adoptive Immuno- therapy for the Methods in Molecular Medicine™ series. Experts from various fields contributed to this comprehensive collection of state-of-the-art methods for adoptive immunotherapy. Recent technical advances and specific methods from the areas of dendritic cell therapy, generation of anti- gen-specific cytotoxic T cells, and antitumor treatment with specific antibodies have been compiled. Particular emphasis is placed on preclinical and clinical applications. These chapters are complemented by articles describing the progress of selected approaches in clinical trials. Leading experts in the field provide theoretical overviews and point out future directions for the improve- ment of adoptive immunotherapy. Additional chapters on the molecular defini- tion of target antigens, mathematical modeling approaches to immunotherapy, and the utilization of regulatory T cells complete the volume. We were fortunate to receive support from leading scientists from all over the world who contrib- uted their most recent experimental protocols and shared their practical advice. Special emphasis was placed on the “Notes” section to include helpful trouble- shooting advice for daily work at the lab bench, which is a unique feature of the Methods in Molecular Medicine™ series. It is our hope that we have achieved our main objective to provide helpful information for scientists just entering the field of adoptive immunotherapy. Furthermore, this volume attempts to encour- age more experienced researchers to try novel experimental approaches. We are indebted to all our authors for generously making their time avail- able in contributing to this volume and for the excellent quality of their work. Marcel Kremer’s help in the final editing process is greatly appreciated. Finally, we want to thank the Series Editor, John Walker, and the staff of Humana Press for their support and continuous encouragement. Burkhard Ludewig Matthias Hoffmann v vi Preface Contents Preface ..............................................................................................................v Contributors .....................................................................................................xi 1 Exploiting Dendritic Cells for Active Immunotherapy of Cancer and Chronic Infection David O’Neill and Nina Bhardwaj.......................................................1 2 A Mathematical Approach for Optimizing Dendritic Cell-Based Immunotherapy Gennady Bocharov, Neville J. Ford, and Burkhard Ludewig.............19 3 Delivery of Tumor Antigens to Dendritic Cells Using Biodegradable Microspheres Ying Waeckerle-Men, Bruno Gander, and Marcus Groettrup...........35 4 RNA Transfection of Dendritic Cells Frank Grünebach, Martin R. Müller, and Peter Brossart...................47 5 Isolation and Generation of Clinical-Grade Dendritic Cells Using the CliniMACS System John D. M. Campbell, Christoph Piechaczek, Gregor Winkels, Edith Schwamborn, Daniela Micheli, Sonja Hennemann, and Jürgen Schmitz.........................................................................55 6 Generation of Clinical Grade Monocyte-Derived Dendritic Cells Using the CliniMACS System Thomas Putz, Hubert Gander, Reinhold Ramoner, Claudia Zelle-Rieser, Andrea Rahm, Walter Nussbaumer, Georg Bartsch, Lorenz Höltl, and Martin Thurnher......................71 7 Adenoviral Transduction of Dendritic Cells Rienk Offringa, Kitty Kwappenberg, Martijn Rabelink, Delphine Rea, and Rob Hoeben.....................................................83 8 Generation of Autologous Peptide- and Protein-Pulsed Dendritic Cells for Patient-Specific Immunotherapy David O’Neill and Nina Bhardwaj.....................................................97 9 Phenotypical and Functional Characterization of Clinical-Grade Dendritic Cells I. Jolanda M. de Vries, Gosse J. Adema, Cornelis J. A. Punt, and Carl G. Figdor........................................................................113 10 Dendritic Cells in Clinical Trials for Multiple Myeloma Volker L. Reichardt and Peter Brossart............................................127 vii viii Contents 11 Identification of Tumor-Associated Autoantigens With SEREX Özlem Türeci, Dirk Usener, Sandra Schneider, and Ugur Sahin.............................................................................137 12 Application of Proteomics and Protein Analysis for Biomarker and Target Finding for Immunotherapy Petra Weingarten, Petra Lutter, Andreas Wattenberg, Martin Blueggel, Sonja Bailey, Joachim Klose, Helmut E. Meyer, and Christoph Huels.......................................155 13 Isolation and Expansion of Tumor-Reactive Cytotoxic T-Cell Clones for Adoptive Immunotherapy Helga Bernhard, Burkhard Schmidt, Dirk H. Busch, and Christian Peschel...................................................................175 14 Tracking Adoptively Transferred Antigen-Specific T-Cells With Peptide/MHC Multimers Norbert Meidenbauer and Andreas Mackensen...............................185 15 Gene Transfer of MHC-Restricted Receptors Helmut W. H. G. Kessels, Monika C. Wolkers, and Ton N. M. Schumacher..........................................................201 16 Immunotherapy With CTL Restricted by Nonself MHC Liquan Gao, Anne-Marie Downs, and Hans J. Stauss.......................215 17 Designing TCR for Cancer Immunotherapy Ralf-Holger Voss, Jürgen Kuball, Matthias Theobald.......................229 18 Isolation and Expansion of Tumor-Specific CD4+ T-Cells by Means of Cytokine Secretion Christian Becker................................................................................257 19 Methods for the Ex Vivo Characterization of Human CD8+ T Subsets Based on Gene Expression and Replicative History Analysis Nathalie Rufer, Patrick Reichenbach, and Pedro Romero...............265 20 Regulatory T Cells in Antitumor Therapy: Isolation and Functional Testing of CD4+CD25+ Regulatory T-Cells Helmut Jonuleit and Edgar Schmitt..................................................285 21 Monoclonal Antibody-Based Strategies in Autoimmunity and Transplantation Lucienne Chatenoud.........................................................................297 22 Producing Bispecific and Bifunctional Antibodies Dipankar Das and Mavanur R. Suresh..............................................329 23 Antibody–Cytokine Fusion Proteins for the Therapy of Cancer Gustavo Helguera and Manuel L. Penichet......................................347 Contents ix 24 Synthesis and Biological Evaluation of a Paclitaxel Immunoconjugate Ahmad Safavy and Kevin P. Raisch...................................................375 25 Cytotoxic Tumor Targeting With scFv Antibody-Modified Liposomes Cornelia Marty and Reto A. Schwendener.......................................389 26 Intravenous Immunoglobin Treatment for Fibrosis, Atherosclerosis, and Malignant Conditions Ilan Krause and Yehuda Shoenfeld...................................................403 27 Study of T-Cell Costimulatory Blockade In Vivo at a Single Cell Level Minh Diem Vu and Xian Chang Li....................................................409 28 Stem Cell Transplantation: Graft-Mediated Antileukemia Effects William J. Hogan and Hans Joachim Deeg.......................................421 29 Influence of Radiation Protocols on Graft-vs-Host Disease Incidence After Bone-Marrow Transplantation in Experimental Models Sebastian Schwarte and Matthias W. Hoffmann..............................445 30 Induction of Chimerism and Tolerance Using Freshly Purified or Cultured Hematopoietic Stem Cells in Nonmyeloablated Mice Nikos Emmanouilidis and Christian P. Larsen..................................459 31 Induction of Mixed vs Full Chimerism to Potentiate GVL Effects After Bone-Marrow Transplantation Markus Y. Mapara and Megan Sykes................................................469 32 Application of Donor Lymphocytes Expressing a Suicide Gene for Early GVL Induction and Later Control of GVH Reactions After Bone-Marrow Transplantation Attilio Bondanza, Fabio Ciceri, and Chiara Bonini..........................475 Index............................................................................................................487