Therapeutic Antibody Engineering

The field of antibody engineering has become a vital and integral part of making new, improved next generation therapeutic monoclonal antibodies, of which there are currently more than 300 in clinical trials across several therapeutic areas. Therapeutic antibody engineering examines all aspects of engineering monoclonal antibodies and analyses the effect that various genetic engineering approaches will have on future candidates. Chapters in the first part of the book provide an introduction to monoclonal antibodies, their discovery and development and the fundamental technologies used in their production. Following chapters cover a number of specific issues relating to different aspects of antibody engineering, including variable chain engineering, targets and mechanisms of action, classes of antibody and the use of antibody fragments, among many other topics. The last part of the book examines development issues, the interaction of human IgGs with non-human systems, and cell line development, before a conclusion looking at future issues affecting the field of therapeutic antibody engineering. Goes beyond the standard engineering issues covered by most books and delves into structure-function relationships Integration of knowledge across all areas of antibody engineering, development, and marketing Discusses how current and future genetic engineering of cell lines will pave the way for much higher productivity

Still the most comprehensive reference source on the development, production and therapeutic application of antibodies, this second edition is thoroughly updated and now has 30% more content. Volume 1 covers selection and engineering strategies for new antibodies, while the second volume presents novel therapeutic concepts and antibodies in clinical study, as well as their potential. Volumes 3 and 4 feature detailed and specific information about each antibody approved for therapeutic purposes, including clinical data. This unique handbook concludes with a compendium of marketed monoclonal antibodies and an extensive index. Beyond providing current knowledge, the authors discuss emerging technologies, future developments, and intellectual property issues, such that this handbook meets the needs of academic researchers, decision makers in industry and healthcare professionals in the clinic.

This highly readable textbook serves as a concise and engaging primer to the emerging field of antibody engineering and its various applications. It introduces readers to the basic science and molecular structure of antibodies, and explores how to characterize and engineer them. Readers will find an overview of the latest methods in antibody identification, improvement and biochemical engineering. Furthermore, alternative antibody formats and bispecific antibodies are discussed. The book’s content is based on lectures for the specializations “Protein Engineering” and “Medical Biotechnology” within the Master’s curriculum in “Biotechnology.” The lectures have been held at the University of Natural Resources and Life Sciences, Vienna, in cooperation with the Medical University of Vienna, since 2012 and are continuously adapted to reflect the latest developments in the field. The book addresses Master’s and PhD students in biotechnology, molecular biology and immunology, and all those who are interested in antibody engineering.

70-chapter authoritative reference that covers therapeutic monoclonal antibody discovery, development, and clinical applications while incorporating principles, experimental data, and methodologies. First book to address the discovery and development of antibody therapeutics in their entirety. Most chapters contain experimental data to illustrate the principles described in them. Authors provide detailed methodologies that readers can take away with them and use in their own laboratories.

A valuable resource for researchers and workers in the fields of both pharmaceuticals and biotechnology as well as undergraduates in biochemistry, applied biology, biomedical sciences and pharmacy, this book compares established techniques of antibody production with the new. Antibody structure and the implications of antibody engineering are fully discussed, and a case study approach illustrates how antibodies are finding increasing use in the diagnosis and treatment of disease. The volume ends with commercial expression, purification and large-scale manufacture of antibodies and their future potential, particularly as therapeutic agents.

Soon after the first description of monoclonal antibodies in 1976, there was enormous interest in the clinical application of antibodies, especially in the context of cancer. Antibodies appeared to offer the “magic bullet” that would allow the specific destruction of neoplastic cells. H- ever, many years’ effort resulted in very few cases of successful immu- therapy with antibodies. As a result there was a major backlash against antibody therapy, and the field lost a considerable amount of popularity. Fashion, in science as well as in other things, tends to be cyclical. Antibody-based therapy is once again attracting scientists and clinicians. There are several reasons for the renewed optimism; certainly the expe- ence of the last two decades has provided a wealth of information about problems associated with antibody therapy, and possible solutions to these problems. Recombinant antibody engineering has rejuvenated the field, allowing both the modification of antibodies to improve their in vivo pr- erties and the isolation of novel antibody molecules by such techniques as phage display. The results of recent clinical trials have demonstrated unequivocally the benefit of antibody therapy in a number of settings, and, finally, more careful consideration has been taken of the types of disease best treated using this approach.

The last decade has witnessed remarkable developments in antibody research and its therapeutic applications. With the methods of molecular biology it is now possible to manipulate the specificities and activities of antibody molecules to generate an almost limitless array of structures for both basic investigations and the clinical setting. The contributions to this volume cover all three domains of the antibody: the variable regions, the relatively neglected but crucial hinge, and the constant region. These studies provide critical structural and functional information about antibodies, while also pointing the way to the construction of molecules with enhanced or even novel properties. Bringing together major experts on antibody engineering, this book is highly recommended to faculty, postdoctoral fellows and graduate students in molecular biology, microbiology, immunology, cancer research and genetics.

Over 2000 years ago in China, antibodies elicited by early forms of vaccination likely played a major role in the protection of the population from infectious agents. Vac- nation has been further developed in Europe and described by Edward Jenner in the late-eighteenth century, then successfully implemented worldwide. The idea to use theactiveingredientinthebloodofvaccinated(orimmunized)animalsorhumansfor the treatment of diseases came a century later. It was made possible by a series of discoveries,suchastherealizationthattheserumfromanimalsimmunizedwithtoxins, for example, diphtheria toxin or viruses, is an effective therapeutic against the disease causedbythesameagentinhumans. Inthe1880s,vonBehringdevelopedanantitoxin (anti-body) that did not kill the bacteria but neutralized the bacterial toxin. The first Nobel Prize in Medicine (1901) was given to him for the discovery of the serum therapy. Acenturylater,22monoclonalantibodies(mAbs)areapprovedbytheUnited States Food and Drug Administration (FDA) for clinical use, and hundreds are in clinicaltrialsforthetreatmentofvariousdiseasesincludingcancers,immunedisorders, and infections. The revenues from the top-five therapeutic antibodies reached $11. 7 billion in 2006, and major pharmaceutical companies raced to acquire antibody biotech companies with a recent example of MedImmune, Inc. , which was acquired for $15. 6 billion by AstraZeneca in 2007. This explosion of research and development in the field of therapeutic antibodies prompted the publication of the MiMB volume Therapeutic Antibodies: Methods and Protocols. The book’s major goal is to present a set of protocols useful for researchers discoveringanddevelopingtherapeuticantibodies. Currentadvancesandfuturetrends in the antibody therapeutics are analyzed in the lead-in review article.