Diagnostic And Therapeutic Antibodies

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.

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.

The American Anti-Vivisection Society (AAVS) petitioned the National Institutes of Health (NIH) on April 23, 1997, to prohibit the use of animals in the production of mAb. On September 18, 1997, NIH declined to prohibit the use of mice in mAb production, stating that "the ascites method of mAb production is scientifically appropriate for some research projects and cannot be replaced." On March 26, 1998, AAVS submitted a second petition, stating that "NIH failed to provide valid scientific reasons for not supporting a proposed ban." The office of the NIH director asked the National Research Council to conduct a study of methods of producing mAb. In response to that request, the Research Council appointed the Committee on Methods of Producing Monoclonal Antibodies, to act on behalf of the Institute for Laboratory Animal Research of the Commission on Life Sciences, to conduct the study. The 11 expert members of the committee had extensive experience in biomedical research, laboratory animal medicine, animal welfare, pain research, and patient advocacy (Appendix B). The committee was asked to determine whether there was a scientific necessity for the mouse ascites method; if so, whether the method caused pain or distress; and, if so, what could be done to minimize the pain or distress. The committee was also asked to comment on available in vitro methods; to suggest what acceptable scientific rationale, if any, there was for using the mouse ascites method; and to identify regulatory requirements for the continued use of the mouse ascites method. The committee held an open data-gathering meeting during which its members summarized data bearing on those questions. A 1-day workshop (Appendix A) was attended by 34 participants, 14 of whom made formal presentations. A second meeting was held to finalize the report. The present report was written on the basis of information in the literature and information presented at the meeting and the workshop.

A detailed, A-Z guide and an indispensable source for pathologists ensuring correct application of immunohistochemistry in daily practice.

An updated edition provides a comprehensive list of antisera and monoclonal antibodies that have useful diagnostic applications.

Monoclonal antibodies have had their impact on biomedical research for more than a decade. Beside their exuberant use as reagents, quite a number of diagnostic and therapeutic approaches have been followed and an impressive number of technological improvements, e.g., humanization, recombinant miniantibodies, have been elaborated to strengthen the principle. With respect to clinical applications, the first generation of antibody 'drugs' is yielding promising results while second and third generation antibody constructs are already underway. The book reviews the status of technological development and brings this into the perspective of clinical results. A rapidly growing amount of clinical data is collected in an expanding number of indications. Hence, the review of clinical study results has been grouped according to the fields of oncology and of chronic and acute inflammation. This book will be of interest to scientists working in the fields of oncology, immunology, internal medicine and clinical chemistry.

Antibody Engineering comprises in vitro selection and modification of human antibodies including humanization of mouse antibodies for therapy, diagnosis, and research. This book comprises an overview about the generation of antibody diversity and essential techniques in antibody engineering: construction of immune, naive and synthetic libraries, all available in vitro display methods, humanization by chain shuffling, affinity maturation techniques, de novo synthesis of antibody genes, colony assays for library screening, construction of scFvs from hybridomas, and purification of monoclonal antibodies by exclusion chromatography. In addition, other topics that are discussed in this book are application and mechanism of single domain antibodies, structural diversity of antibodies, immune-mediated skin reactions induced by TNF-alpha recombinant antibodies, and bioinformatic approaches to select pathogen-derived peptide sequences for antibody targets.