Rat Hybridomas and Rat Monoclonal Antibodies Editor Herve Bazin Professor Experimental Immunology Unit Catholic University of Louvain Brussels, Belgium and Commission of the European Communities Directorate-General for Science Research and Development Brussels, Belgium First published 1990 by CRC Press Taylor & Francis Group 6000 Broken Sound Parkway NW, Suite 300 Boca Raton, FL 33487-2742 Reissued 2018 by CRC Press © 1990 by Taylor & Francis CRC Press is an imprint of Taylor & Francis Group, an Informa business No claim to original U.S. Government works This book contains information obtained from authentic and highly regarded sources. Reasonable efforts have been made to publish reliable data and information, but the author and publisher cannot assume responsibility for the validity of all materials or the consequences of their use. 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ISBN 13: 978-1-138-50610-7 (hbk) ISBN 13: 978-0-203-71057-9 (ebk) Visit the Taylor & Francis Web site at http://www.taylorandfrancis.com and the CRC Press Web site at http ://www. crcpress. com PREFACE Professor Joseph Maisin, to whose memory this book is dedicated, was a flamboyant personality. With the help of wealthy patients and other patrons, as early as 1925 he had built a large, modem Cancer Institute in the Louvain Medical School. Three floors of the building were occupied by wards, operating theatres, examination rooms, and radiotherapy equipment, including a unique radium bomb donated by the Union Miniere du Haut-Katanga, the main mining company in the Belgian Congo. Laboratories and offices filled the ground floor. The greater part of the basement housed thousands of mice and rats. With ventilation being what it was in those days, this was not an ideal situation from the point of view of the patients, but Maisin saw the inconvenience as their personal contribution to the research aimed at improving their lot. I lived in this Institute during three war years, serving as “full-time” clinical assistant to the boss, yet enjoying enough freedom to earn a master’s degree in chemistry at the university. It is typical of Maisin’s broadmindedness and vision that he approved of this strange arrangement. Joining the resources of medicine and chemistry would produce what he felt would be the science of the future and, in his eyes, was a sufficient reason for supporting my undertaking. Maisin was a distinguished pathologist and an outstanding clinician, who took care of his patients with remarkable competence and dedication. Patients flocked to him from all over the country and elsewhere, yet I never saw him cutting an examination short or even failing to give comfort and hope for lack of time. His enormous vitality made up the gaps and allowed him to devote his energies to many extra-clinical activities. He was one of the founders of the International Union Against Cancer, of which he was successively Secretary General, President, and Honorary President, and edited its Acta for many years. He was involved in many other organizations, national and international, and traveled a great deal. He had a heavy teaching load and interrogated hundreds of students every year. He was an eloquent and charismatic speaker and used the teaching of histopathology as a means of conveying the latest discoveries of medical science to his students. Even so, he still found time for research, of all his activities the closest to his heart. Every evening, after finishing the rounds of his patients, he would go down to the basement to inspect his beloved mice and rats. I confess that I was not much attracted to his brand of research. Groups of animals were put on different diets or given various dietary supplements or injections, chosen with a sometimes dismaying eclecticism. The mice had a patch of skin painted with benzopyrene or methylcholanthrene, whereas the rats were fed the liver carcinogen 4- dimethylamino-azobenzene (butter yellow). Maisin followed with care the frequency, aspect, and development of precancerous and cancerous lesions in the various groups, in the hope of discovering “problastic” or “antiblastic” substances. The approach was too empirical for my taste. However, in the light of today’s epidemiological investigations on the relation between diet and cancer, Maisin now appears to be an authentic pioneer. It was in this celebrated basement that the ancestral couple of the LOU rats first arrived, presumably from the U.S. some time between 1937 and 1941. As related by Herve Bazin in the second chapter of this book, they turned out to be the bearers of a remarkable form of immunocytoma, which was first discovered by Maisin and his co-workers in the early 1950s. The LOU rats have since produced a huge progeny, and with them an impressive body of research, which includes the development of hybridomas and of monoclonal antibodies. They have thereby earned the rat a respectable place in immunology, a discipline known to be somewhat mouse-biased. When Dr. Bazin asked me to write a foreword to this book, my first reaction was to say no. Even in the most charitable context, I could not possibly qualify as an immunologist nor as an expert on monoclonal antibodies. He kindly insisted and I finally accepted his invitation, seeing in it an opportunity to recall the memory of a remarkable man for whom I had great respect, affection, and gratitude. No doubt, Joseph Maisin would have welcomed with enthusiasm the publication of this book, the topic of which, through the strange and devious ways of science, he unknowingly initiated some 50 years ago. Christian de Duve Nobel Prize 1974 ACKNOWLEDGMENTS We are indebted to a large number of individuals: B. de Sejoumet, F. Flemal, M. Godichelle, B. Libert, D. Bourgois, M. Calier, J. De Mets, L. De Clercq, B. De Keyser, T. Goffart, P. Grognet, D. Jourdain, R. Meykens, C. Negel, J. Relies, and L. M. Xhurdebise who worked more or less a long time in the Experimental Immunology Unit. They all have largely contributed to the development of the LOUVAIN rat model in collaboration with those who have written sections of this book and with many distinguished colleagues who have participated to parts of these studies, in particular the late Prof. J. F. Heremans, C. Milstein, A. Beckers, H. Bennich, J. D. Capra, D. Carson, P. Carter, J. M. Davie, C. Deckers, F. Dessy, A. Froese, M. Fougereau, H. H. Fudenberg, G. Fust, J. Gergely, I. C. M. MacLennan, G. A. Medgyesi, H. Metzger, M. Moriame, R. Pauwels, I. Schechter, D. Secher, A. H. Sehon, H. L. Spiegelberg, V. Starace, J. Urbain, J. P. Vaerman, and A. C. Wang. The idea for a book especially devoted to “Rat Hybridomas and Rat Monoclonal Antibodies” was conceived during a course on that subject given in 1986 at the Beijing Institute for Cancer Research by four members of the Experimental Immunology Unit of the Catholic University of Louvain, under the auspices of a collaboration between these Institutes and the National Center for Biotechnology of the People’s Republic of China and the Commission of the European Communities, Division for Science, Research and Development. We particularly thank Profes­ sors Yonghui Liu, Zhi-Wei Dong, Yong-Su Zhen, P. Fasella, G. Valentini, F. Van Hoeck, S. Finzi, G. Gerber, and D. de Nettancourt for their help and encouragement in the implementation of this collaboration which we hope will continue for years to come and contribute to developing scientific cooperation and friendship between the People’s Republic of China and the European Communities. Studies on rat immunocytomas began with the financial support of the “Fonds Cancerolo- gique de la Caisse Generale d’Epargne et de Retraite” Belgium to whom we are particularly indebted. Their support was determining at the beginning of these studies and very useful throughout their development. We also received funds from the “Fonds National de la Recherche Scientifique” (Belgium), the “Fonds de la Recherche Medicale” (Belgium), the Radiation Protection Research Programme of the CEC (Publication 2459), the “National Institute of Health” (U.S.A.), the “Institut National de la Sante et de la Recherche Medicale” (France), the “Delegation Generale a la Recherche et aux Sciences et Techniques” (France), the Institut pour I'Encouragement de la Recherche Scientifique dans l’lndustrie et l’Agriculture” (Belgium), the “Service de Programmation de la Politique Scientifique” (Belgium), and the Bekales Foundation (Liechtenstein). They have all contributed to the development of the LOUVAIN rat model and also the Directorate-General Division for Science, Research and Development of the Commission of the European Communities of which I have been a scientific staff member for 20 years. I am especially indebted to F. Bolle, secretary of the unit, who has tirelessly prepared the manuscript of this book and improved the final draft. I wish to acknowledge N. Gardiner for supervising the English text. My thanks are also to L. De Greef, who often alone assumed the secretarial tasks of the unit during the last months of preparation of this manuscript and finally to M. Brancart, who has paid meticulous attention to the unit finances. Herve Bazin DEDICATION To the late Professor Joseph Maisin, who brought the ancestors of LOUVAIN rats to the Catholic University of Louvain and worked many years with them. This small rat nucleus has now developed into a large breed which lives throughout the world. CONTRIBUTORS Fabienne Ackermans Andre Capron Assistant Professor Professor, Head Experimental Immunology Unit Institut Pasteur de Lille Faculty of Medicine Centre d’lmmunologie et de Biologie University of Louvain Parasitaire Brussels, Belgium Unite Mixte INSERM Lille, France Herve Bazin Monique Capron Professor, Head Associate Professor Experimental Immunology Unit Centre d’lmmunologie et de Biologie Faculty of Medicine Parasitaire University of Louvain Unite Mixte INSERM 167 — CNRS 624 Brussels, Belgium Lille, France Blanche Bellon Andreas Cerny Research Fellow Research Assistant Pathologie Renale et Vasculaire Institute of Pathology INSERM U28 Experimental Pathology Hopital Broussais University Hospital Paris, France Zurich, Switzerland Monique Bodeus Danielle Chassoux Research Assistant Charge de Recherches Microbiology Unit Institut de Recherches Scientifiques sur le Faculty of Medicine Cancer University of Louvain CNRS ER 278 Brussels, Belgium Villejuif, France Erik Briers Marcela-Viviana Chazev General Director Experimental Immunology Unit N. V. Eco-Bio Faculty of Medicine Genk, Belgium University of Louvain Brussels, Belgium Yveline Bruinen Francoise Cormont Executive Secretary of the European Node Research Assistant CERDIC Experimental Immunology Unit Faculte de Medecine Faculty of Medicine Chemin de Vallombrose University of Louvain Nice, France Brussels, Belgium Guy Burtonboy Guy Cornelis Associate Professor Associate Professor Microbiology Unit Microbiology Unit Faculty of Medicine Faculty of Medicine University of Louvain University of Louvain Brussels, Belgium Brussels, Belgium Anne Cornet Claire Durieux Technician Institut Pasteur de Lille Haematology Unit SERLIA University of Louvain Lille, France Brussels, Belgium Beatrice Dutertre Marc De Bruyere Scientific Attache of the European Node Professor, Head, CERDIC Immuno-Haematology Unit Faculte de Medecine Faculty of Medicine Chemin de Vallombrose University of Louvain Nice, France Brussels, Belgium Jia-Chun Fang Alain De Cremer Research Assistant Technician Beijing Institute for Cancer Resarch Experimental Immunology Unit Beijing, People’s Republic of China Faculty of Medicine University of Louvain Catherine Fievet Brussels, Belgium Charge de Recherches a 1’INSERM Institut Pasteur de Lille Thierry Delaunay SERLIA Research Associate Lille, France Hoechst-Behring (France) Experimental Immunology Unit Jean-Charles Fruchart Faculty of Medicine Professor, Director University of Louvain SERLIA Brussels, Belgium Institut Pasteur de Lille Lille, France Nicole Delferriere Research Associate Christine Genart Microbiology Unit Technician Faculty of Medicine Experimental Immunology Unit University of Louvain Faculty of Medicine Brussels, Belgium University of Louvain Brussels, Belgium Colette Digneffe Research Associate Agnes Goris Experimental Immunology Unit Research Associate Faculty of Medicine N.V. Eco-Bio University of Louvain Genk, Belgium Brussels, Belgium Jean-Marie Grzych Philippe Druet Research Assistant Professor, Head, Institut Pasteur de Lille Pathologie Renale et Vasculaire Centre dTmmunologie et de Biologie INSERM U28 Parasitaire Hopital Broussais Unite Mixte INSERM 167 — CNRS 624 Paris, France Lille, France Jean-Charles Guery Dominque Latinne Graduate Student Immuno-Haematology Unit Pathologie Renale et Vasculaire Haematology Unit INSERM U28 Faculty of Medicine Hopital Broussais University of Louvain Paris, France Brussels, Belgium Francois Hirsch Research Fellow Marc Lefebvre Pathologie Renale et Vasculaire Research Assistant INSERM U28 Experimental Immunology Unit Hopital Broussais Faculty of Medicine Paris, France University of Louvain Brussels, Belgium Josee Hutschemackers Research Associate Anne-Marie Lebacq-Verheyden Phytopathology Unit Haematology Unit Faculty of Agronomic Sciences Faculty of Medicine University of Louvain University of Louvain Louvain-La-Neuve, Belgium Brussels, Belgium Michele Janssens Research Associate L. G. Linares-Cruz Microbiology Unit Research Assistant Faculty of Medicine Institut de Recherches Scientifiques sur le University of Louvain Cancer Brussels, Belgium CNRS ER 278 Villejuif, France Min Jiang Research Associate Jean-Marie Malache Institute of Medicinal Biotechnology Experimental Immunology Unit Chinese Academy of Medical Sciences Faculty of Medicine Tiantan University of Louvain Beijing, People’s Republic of China Brussels, Belgium Jean-Pierre Kints Animal House Manager Patrick Manouvriez Experimental Immunology Unit Research Associate Faculty of Medicine Experimental Immunology Unit University of Louvain Faculty of Medicine Brussels, Belgium University of Louvain Brussels, Belgium George Klein Professor G. M. Marchal Department of Tumor Biology Laboratory of Pathology and Microbiology Karolinska Institute Thuin, Belgium Stockholm, Sweden Monique Koffigan Ludo Meulemans Institut Pasteur de Lille Development Manager SERLIA N.V. Eco-Bio Lille, France Genk, Belgium