Bispecific Antibodies
The concept of using bispecific antibodies for cancer therapy by retargeting immune effector cells was developed more than 25 years ago. However, initial clinical studies were rather disappointing mainly due to low efficacy, severe side effects and the im
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Bispecific Antibodies
Bispecific Antibodies
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Roland E. Kontermann Editor
Bispecific Antibodies
Editor Dr. Roland E. Kontermann Universita¨t Stuttgart Inst. fu¨r Zellbiologie und Immunologie Allmandring 31 70569 Stuttgart Germany [email protected]
ISBN 978-3-642-20909-3 e-ISBN 978-3-642-20910-9 DOI 10.1007/978-3-642-20910-9 Springer Heidelberg Dordrecht London New York Library of Congress Control Number: 2011933913 # Springer-Verlag Berlin Heidelberg 2011 This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilm 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 current version, and permission for use must always be obtained from Springer. Violations are liable to prosecution under the German Copyright Law. 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. Printed on acid-free paper Springer is part of Springer Science+Business Media (www.springer.com)
Preface
The first description of bispecific antibodies dates back 50 years, when Nisonoff and Rivers described the recombination of a mixture of univalent antibody fragments of different specificity. However, it took another 20 years before bispecific antibodies were proposed for therapeutic applications, mainly for the retargeting of effector T cells to tumor cells. These early studies implied already the use of bispecific antibodies to extend the functions beyond that normally executed by antibodies. Limited by the availability of monoclonal antibodies obtained from animal sources, bispecific antibodies of this early phase were generated by somatic hybridization of two hybridomas or by chemical conjugation of two IgG molecules. The high expectations on these bispecific antibodies were, however, not fulfilled, mainly because of low efficacy, immunogenicity, and severe adverse effects seen in clinical trials. This resulted in a loss of interest in this kind of molecules during the last decade of the last century. However, with advancements in antibody engineering and the establishment of novel applications, bispecific antibodies experienced a revival at the beginning of this century. Besides effector cell retargeting for cancer immunotherapy, applications include, among others, pre-targeting strategies in radioimmunotherapy and more recently dual-targeting strategies simultaneously attacking two disease-relevant targets. Genetic engineering allows nowadays to generate recombinant bispecific antibodies of defined composition, as well as with improved stability and producibility. Hence, bispecific ant
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