Monoclonal Antibodies And Their Functional Fragments In Research Diagnosis And Therapy

Monoclonal antibodies (mAbs) are among the most specialised molecules for the recognition and capture of specific analytes. Hundreds of thousands of mAbs have been generated for a large number of different antigens with increasing affinity and specificity and are available for the most diverse purposes. Many of them have been validated as irreplaceable agents for diagnosis and therapy or as unique reagents for research. Others have been developed using emerging technologies that avoid the need for animal immunisation. This short book strives to gather the perspective view of the various contributing authors and to survey the new strategic assets adopted to generate novel monoclonal antibodies or surrogates, such as Fab, Fab2, ScFv and nanobodies, which have an increasing impact in biomedicine as therapeutic or diagnostic assets in various diseases.

It has been almost 20 years since the discovery by Kohler and Milstein of the technology to produce monoclonal antibodies (MAbs), a discovery that promised revolutionary changes in research, clinical diagnosis and human therapy. From today's perspective, it is fair to conclude that this promise has been realized in two areas of the three. As research tools, MAbs have been invaluable: their ability to selectively bind and localize specific antigens, detect and identify new ligands and their receptors, and agonize and/or antagonize specific molecular interactions continues to provide a useful and enabling technology to basic research endeavors. Similarly, MAbs have demonstrated enormous practical impact as diagnostic tools. Recent advances in clinical diagnostic medicine continue to rely heavily on the use of MAb-based reagents for detecting and localizing antigens of clinical import. In contrast, however, MAbs have not proven to have major impact on human disease therapy. With the single exception of an immunosup pressive MAb against the T-cell antigen, CD3, MAbs have as yet found few meaningful applications as therapeutic agents. During the 1980s, a set of technologies to clone, modify and express genes encoding MAbs was developed. These breakthroughs permitted MAbs to be genetically engineered which consequently gave them the potential to greatly enhance their therapeutic utility as well as significantly expand their research and diagnostic applications. New MAbs, fragments of MAbs, bispecific MAbs, single-chain MAbs, and fusions of MAbs with other gene products became available for study.

The book broadly deals with therapeutic monoclonal antibodies (mAbs) and various relevant topics, including different antibody formats such as Antibody-Drug Conjugates (ADC), bispecifics, nanoparticle-based mAbs and HER2+ cancers, immune checkpoint inhibitors and other closely related topics. Each paper was written by leading active research groups in their fields both from academia and industry. The book should be of interest to those scientists and researchers who develop or use biologics, biotherapeutics, biosimilars and biobetters in cancer treatment.

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.

The book deals with therapeutic monoclonal antibodies (mAbs) broadly, and relevant topics such as challenges and opportunities, next-generation antibody products, Antibody-Drug-Conjugates (ADC), bispecifics, glycosylation, and T-cell engagers are covered. Each topic has been written by leading groups around the world and the book should be of interest to researchers from both academia and industry.

Monoclonal antibodies (mAbs) are naturally occurring complex biomolecules. New engineering methods have turned mAbs into a leading therapeutic modality for addressing immunotherapeutic challenges and led to the rise of mAbs as the dominant class of protein therapeutics. mAbs have already demonstrated a great potential in developing safe and reliable treatments for complex diseases and creating more affordable healthcare alternatives. Developing mAbs into well-characterized antibody therapeutics that meet regulatory expectations, however, is extremely challenging. Obstacles to overcome include the determination and development of physiochemical characteristics such as aggregation, fragmentation, charge variants, identity, carbohydrate structure, and higher-order structure (HOS). This book dives deep into mAbs structure and the array of physiochemical testing and characterization methods that need to be developed and validated to establish a mAb as a therapeutic molecule. The main focus of this book is on physiochemical aspects, including the importance of establishing quality attributes such as glycosylation, primary sequence, purity, and HOS and elucidating the structure of new antibody formats by mass spectrometry. Each of the aforementioned quality attributes has been discussed in detail; this will help scientists in researching and developing biopharmaceuticals and biosimilars to find practical solutions to physicochemical testing and characterization. Describes the spectrum of analytical tests and characterization methods necessary for developing and releasing mAb batches Details antibody heterogeneity in terms of size, charge, and carbohydrate content Gives special focus to the structural analysis of mAbs, including mass spectrometry analysis Presents the basic structure of mAbs with clarity and rigor Addresses regulatory guidelines - including ICH Q6B - in relation to quality attributes Lays out characterization and development case studies including biosimilars and new antibody formats

This book aims to provide a unique combination of the production (by both cellular and molecular biology techniques), structure and functional characteristics of monoclonal antibodies, together with detailed discussions of the various analytic, diagnostic and therapeutic applications.