CELLULAR ENGINEERING AND CELLULAR THERAPIES

CELLULAR ENGINEERING AND CELLULAR THERAPIES

DEVELOPMENTS IN HEMATOLOGY AND IMMUNOLOGY Volume 38 The titles published in this series are listed at the end a/this volume.

Cellular Engineering and Cellular Therapies Proceedings of the Twenty-Seventh International Symposium on Blood Transfusion, Groningen, Organized by the Sanquin Division Blood Bank North-East, Groningen edited by C.TH. SMIT SIBINGA Sanquin Consulting Services, and L.F.M.H. DE LEU Groningen University Institute for Drug Exploration, Springer-Science+Business Media, B.V.

A c.i.p. Catalogue record for this book is available from the Library of Congress ISBN 978-1-4419-5250-9 ISBN 978-1-4757-3718-9 (ebook) DOI 10.1007/978-1-4757-3718-9 Printed on acid-free paper All Rights Reserved 2003 Springer Science+Business Media Dordrecht Originally published by Kluwer Academic Publishers in 2003. Softcover reprint of the hardcover 1 st edition 2003 No part of this work 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 permission from the Publisher, with the exception of any material supplied specifically for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work.

This 27 th Sanquin International Symposium on Blood Transfusion was supported by WHO and International Society of Blood Transfusion and conducted under the auspices of the Sanquin Blood Supply Foundation. Baxter Acknowledgement This publication has been made possible through the support of Baxter, which is gratefully acknowledged.

VII CONTENTS Moderators and Speakers....IX Foreword... XIII I. DEFINING THE FIELD Cellular Engineering and Cellular Therapies - an Overview... 3 L.F.M.H. de Leij Gene Therapy 2002: A New Start... 11 N.H. Mulder Stem Cells: Potential, Selection and Plasticity... 21 G. de Haan The Potential of Stem Cell Transplantation to Rescue the Failing Liver... 31 P.L.M Jansen Discussion... 35 II. PROCESSING ASPECTS The New Regulatory Environment for Cellular Therapy Products: Challenges for Academic-Based Manufacturing Facilities....45 E.J. Read Biological Modification of Lymphocytes on Auto- and Allo-Immune Diseases... 55 J.W. Semple Cell Harvest and Purification Technology - State of the Art and Future Development... 69 P.Law Cell Manipulation and Engineering - State of the Art and Future Developments... 81 S.l Noga

VIII Cellular Immunotherapy - Towards Direct DC Activation for Licence to Kill... 89 F.A. Ossendorp Discussion... 95 III. QUALITY ASPECTS From Research to Clinical Application - the Quality Concept...... III P.R. Roddie Factors Controlling Expansion and Maturation of Haematopoietic Progenitor Cells... 119 A.L. Drayer Cell Processing for Gene and Cell Therapy Protocols: Limitations and Opportunities!... 133 I. Slaper-Cortenbach Discussion... 139 IV. CLINICAL EXPERIENCES AND PROSPECT FOR TREATMENT State of the Art in Dendritic Cell Vaccination... 153 J. de Vries Reconstituting T Cell Immunity Following Hematopoietic Stem Cell Transplantation... 161 S.R. Solomon State of the Art in Gene Therapy... 171 H.J. Haisma New Horizons in Cellular Therapies... 189 P. Rebulla Cellular Engineering and Cellular Therapies - Transfusion Medicine and the Academic World... 203 C. Th. Smit Sibinga Discussion... 207 Index... 215

IX MODERATORS AND SPEAKERS Moderators L. de Leij (chairman) G.D. M. Beun P.L.M. Jansen H.C. Kluin-Nelemans P.Law F. Miedema S.D. Noga P. Rebulla - Department of Pathology and Laboratory Medicine, Medical Biology Section, University Medical Centre Groningen, and GUIDE, University of Groningen - Sanquin Blood Bank North-East Groningen, NL - Department of Hepatology and Gastroenterology, University Hospital Groningen - Department of Haematology, University Hospital Groningen Director, Cell Process Development Dendreon Corporation Seattle, W A, USA - Sanquin CLB Division Research Amsterdam, The Netherlands - The Johns Hopkins University, and Alvin & Lois Lapidus Cancer Institute, Sinai Hospital of Baltimore Baltimore, MD, USA - Cell Factory 'Franco Calori', Milano Cord Blood Bank, Centro Trasfusionale e di Immunologia dei Trapianti Milan, Italy

x Speakers L.A. Drayer e.g. Figdor G. de Haan H.I. Haisma P.L.M. Jansen P.Law L. de Leij N.H. Mulder S.I. Noga F.A.Ossendorp P. Rebulla - Sanquin Blood Bank North-East Groningen, NL - Center for Molecular Life Sciences, University ofnijmegen Nijmegen, The Netherlands - Department of Stem Cell Biology, University of Groningen - Dept of Therapeutic Gene Modulation, University Center for Pharmacy, University of Groningen - Department of Hepatology and Gastroenterology, University Hospital Groningen - Director, Cell Process Development Dendreon Corporation Seattle, W A, USA - Department of Pathology and Laboratory Medicine, Medical Biology section University Medical Centre Groningen - Dept. of Medical Oncology, University Hospital Groningen - The Johns Hopkins University, and Alvin & Lois Lapidus Cancer Institute, Sinai Hospital of Baltimore Baltimore, MD, USA - Department Immunohematology and Blood Transfusion, Leiden University Medical Center Leiden, The Netherlands - Cell Factory 'Franco Calori', Milano Cord Blood Bank, Centro Trasfusionale e di Immunologie dei Trapianti Milan, Italy

XI E.K. Read P.H. Roddie J.W. Semple I. Slaper-Cortenbach C. Th. Smit Sibinga S. Solomon - Department of Transfusion Medicine, Warren G. Magnusen Clinical Center, National Institutes of Health Bethesda, MD, USA - Consultant Haematologist, Department of Haematology, Western General Hospital Edinburgh, UK - Toronto Platelet Immunobiology Group Toronto, Ontario, Canada - Department of Hematology, University Medical Center Utrecht Utrecht, The Netherlands - Academic Institute for International Development of Transfusion Medicine, University of Groningen, and Sanquin Consulting Services - Stem Cell Allotransplantation Section, Hematology Branch, National Heart, Lung and Blood Institute, NIH Bethesda, MD, USA.

XIII FOREWORD Welcome to the City of Groningen, the center of the North of the Netherlands. Groningen is proud of the long lasting tradition of scientific symposia organised by the Sanquin Blood Bank. These Sanquin International Symposia on Blood Transfusion have become a true traditional event in Groningen, marking the early academic year and have contributed to the specific reputation of Groningen and its University in the scientific field of Transfusion Medicine. The growing tradition has also contributed to initiatives of both University, Province and the City of Groningen to bring science and industry together - BioMedCity Groningen. Such reputation does not just happen, but is the result of creative and scientific leadership, of vision and an open mind, to explore in a team spirit horizons. Groningen is particularly proud of this reputation thanks to its leadership, the Sanquin Blood Bank North-East. This year in particular the theme chosen some two years ago is extremely timely as it illustrates the activities and scientific interest of an integrated team which includes our regional Sanquin Blood Bank North-East and fits in the City initiatives within the concept of BioMedCity, Groningen. Transfusion medicine is the bridging science involved in both the processing and engineering of harvested cells and the response to potential application of cellular therapies - in practice vein to vein. Specifically harvested cells are attractive targets for cellular therapies and gene transfer, because 1. cells can be easily obtained and manipulated, and 2. stem cell transplantation has already been successfully applied for treating a number of genetic disorders. Thus, the transfusion medicine centres of excellence, such as the Sanquin Blood Bank NorthEast in Groningen, should no longer be regarded as simple production facilities but should be academically integrated and become centres for translational research. Since cellular therapies including gene transfer entail both cellular processing and genetic modification under strict pharmaceutical conditions securing optimal quality, there is a need for integrated processing and clinical laboratories where these activities can be carried out and properly managed. In Groningen such an integration has started with an joint endeavour of University, Academic Hospital and Sanquin Blood Bank and will undoubtedly lead to

XIV new developments in cellular engineering and cellular therapies. The City of Groningen has great interest in this project and will support where possible. It is evident that a complex of conditioning requirements need to be fulfilled, including a highly developed infrastructure, cost containment and above all team spirit and leadership. The clinical outcome - the patient care - of a joint effort in an academic setting and an infrastructure climate within the City of Groningen should be based on strictly controlled and well governed production processes for which expertise is available within our city and province. I wish you all a successful symposium and hope to see you back many more times in Groningen to enjoy the science, the city and the culture of the North of the Netherlands. Arnoud Guikema, JD Department of ROEZ Municipality of Groningen