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| Author | : Guido Ferrari |
| Publisher | : Frontiers Media SA |
| Total Pages | : 273 |
| Release | : 2020-07-28 |
| Genre | : |
| ISBN | : 2889638901 |
| Author | : Guido Ferrari |
| Publisher | : Frontiers Media SA |
| Total Pages | : 163 |
| Release | : 2023-05-29 |
| Genre | : Medical |
| ISBN | : 2832524303 |
| Author | : Marije B. Overdijk |
| Publisher | : Elsevier Inc. Chapters |
| Total Pages | : 36 |
| Release | : 2013-08-06 |
| Genre | : Medical |
| ISBN | : 0128060344 |
Historically, lack of specificity for cancer cells has been a major problem in cancer treatment; however, the development of monoclonal antibodies (mAbs), which combine high specificity with multiple mechanisms of action (MoAs), started a revolution in anti-cancer treatment options which continues to date. As of January 2013, 15 major antibody products were being marketed for cancer treatment in various countries around the globe, 10 of which are unmodified mAbs, which generally have multiple potential MoAs and may act via direct, Fab-domain-related effects or indirect, Fc-domain-related effects. Fc-domain-related effects consist of immune-mediated effector functions, which include complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC), and antibody-dependent cellular phagocytosis (ADCP). ADCC and ADCP depend on the engagement of Fcγ-receptors (FcγR) on immune effector cells by Fc-domains clustered due to antibody–antigen binding. Similarly, CDC depends on the engagement of proteins of the complement system by clustered antibody Fc domains. In this chapter, preclinical and clinical studies with approved anti-cancer mAbs are reviewed, with an emphasis on the role of FcγR-mediated effector functions. The importance of therapeutic antibody–FcγR interactions for human treatment can be deduced from correlations of clinical responses with FcγR polymorphisms, results supported by a wealth of preclinical and in vitro studies.
| Author | : Menna R. Clatworthy |
| Publisher | : Elsevier Inc. Chapters |
| Total Pages | : 44 |
| Release | : 2013-08-06 |
| Genre | : Medical |
| ISBN | : 0128060336 |
Fcγ receptors (FcγR) mediate many effector functions of antibody and are critical for defense against pathogens, including bacteria, viruses, and parasites. A number of single nucleotide polymorphisms have been identified in both activating and inhibitory FcγR genes that affect either the binding affinity for IgG or receptor function. Reviewing the available evidence from murine knockout mice, in vitro studies utilizing human cells, and genetic studies in humans, the current view on the role of FcγR polymorphisms in susceptibility to infection will be summarized here. Genetic studies have often yielded conflicting results, which may be due to small sample size or the inherent difficulties associated with genotyping the FCGR locus, or they may reflect differences in the functional importance of interactions between FcγR and its ligands (IgG versus CRP) in differing clinical manifestations of infectious disease. The engagement of the inhibitory FcγR limits the proinflammatory response initiated by FcγR ligation. FCGR polymorphisms that favor activating FcγR may result in excessive inflammation that is deleterious to the host, despite its efficacy in eliminating the pathogen. Overall, pathogen encounter is likely to be the main factor driving the retention of FCGR polymorphisms within the gene pool. Evidence suggests that potent infections, such as malaria, have exerted a significant evolutionary pressure on the maintenance and prevalence of FcγR polymorphisms in different populations.
| Author | : Latha P. Ganesan |
| Publisher | : Frontiers Media SA |
| Total Pages | : 372 |
| Release | : 2020-07-22 |
| Genre | : |
| ISBN | : 2889638758 |
| Author | : Margaret Ackerman |
| Publisher | : Academic Press |
| Total Pages | : 376 |
| Release | : 2013-08-06 |
| Genre | : Medical |
| ISBN | : 0123948185 |
Antibody Fc is the first single text to synthesize the literature on the mechanisms underlying the dramatic variability of antibodies to influence the immune response. The book demonstrates the importance of the Fc domain, including protective mechanisms, effector cell types, genetic data, and variability in Fc domain function. This volume is a critical single-source reference for researchers in vaccine discovery, immunologists, microbiologists, oncologists and protein engineers as well as graduate students in immunology and vaccinology. Antibodies represent the correlate of protection for numerous vaccines and are the most rapidly growing class of drugs, with applications ranging from cancer and infectious disease to autoimmunity. Researchers have long understood the variable domain of antibodies, which are responsible for antigen recognition, and can provide protection by blocking the function of their target antigen. However, recent developments in our understanding of the protection mediated by antibodies have highlighted the critical nature of the antibody constant, or Fc domain, in the biological activity of antibodies. The Fc domain allows antibodies to link the adaptive and innate immune systems, providing specificity to a wide range of innate effector cells. In addition, they provide a feedback loop to regulate the character of the immune response via interactions with B cells and antigen-presenting cells. Clarifies the different mechanisms of IgG activity at the level of the different model systems used, including human genetic, mouse, and in vitro Covers the role of antibodies in cancer, infectious disease, and autoimmunity and in the setting of monoclonal antibody therapy as well as naturally raised antibodies Color illustrations enhance explanations of the immune system
| Author | : Marc Daeron |
| Publisher | : Springer |
| Total Pages | : 426 |
| Release | : 2014-08-12 |
| Genre | : Medical |
| ISBN | : 3319079115 |
This volume provides a state-of-the-art update on Fc Receptors (FcRs). It is divided into five parts. Part I, Old and New FcRs, deals with the long-sought-after FcμR and the recently discovered FCRL family and TRIM21. Part II, FcR Signaling, presents a computational model of FcεRI signaling, novel calcium channels, and the lipid phosphatase SHIP1. Part III, FcR Biology, addresses major physiological functions of FcRs, their glycosylation, how they induce and regulate both adaptive immune responses and inflammation, especially in vivo, FcR humanized mice, and the multifaceted properties of FcRn. Part IV, FcRs and Disease, discusses FcR polymorphism, FcRs in rheumatoid arthritis and whether their FcRs make macaques good models for studying HIV infection. In Part V, FcRs and Therapeutic Antibodies, the roles of various FcRs, including FcγRIIB and FcαRI, in the immunotherapy of cancer and autoimmune diseases using monoclonal antibodies and IVIg are highlighted. All 18 chapters were written by respected experts in their fields, offering an invaluable reference source for scientists and clinicians interested in FcRs and how to better master antibodies for therapeutic purposes.
| Author | : Jan G.J. Winkel |
| Publisher | : Springer Science & Business Media |
| Total Pages | : 320 |
| Release | : 2012-02-02 |
| Genre | : Medical |
| ISBN | : 9401150184 |
Antibodies are crucial to the fine specificity of the immune system. An effective functioning of these molecules requires interaction with immune cells. Receptors for antibodies, Fc receptors, provide this critical link between the humoral and cellular branches of the immune system. This book presents a comprehensive overview of the different Fc receptors currently recognized. The first part of the book contains state-of-the-art overviews on the biological role of FcR. The latest information on FcR heterogeneity, FcR physiology, FcR-ligand recognition, their crucial coordinating role in immunity, interactions with other immunoreceptors, and the role of FcR in immunoglobulin transport and catabolism are discussed. The clinical importance of FcR is developed in the second part of the book. The well-recognized roles of FcR in allergy, inflammation, infectious diseases, autoimmune disorders, and immunotherapeutic importance are reviewed. The information in this book is easily accessible and should be helpful for researchers and clinical specialists as a convenient overview of the field, as well as a comprehensive introduction for students starting in this area of research.
| Author | : Peter Sun |
| Publisher | : Elsevier Inc. Chapters |
| Total Pages | : 30 |
| Release | : 2013-08-06 |
| Genre | : Medical |
| ISBN | : 012806028X |
Molecular mechanisms of antibody-mediated Fc receptor activation have long been an interest in both Fc receptor biology and antibody therapeutics. The structural efforts to elucidate antibody recognition by Fc receptors have led to the generation of several crystal structures of antibody Fc fragments complexed with Fc receptors. Collectively, these structures revealed a conserved receptor binding mode for IgG and IgE, distinct from those for the neonatal Fc receptor (FcRn), protein A, and protein G. Fcγ receptor recognition in the lower hinge region allows enhanced antigen recognition through dimeric Fabs but obligates immune-complex formation for receptor activation. It also provides the basis for Fcγ receptors to differentiate among IgG subclasses. More recently, pentraxins have also been shown to bind and activate Fc receptors, and structural efforts to elucidate pentraxin Fcγ receptor recognition have revealed surprising similarities between pentraxins and immunoglobulins in Fc receptor recognition. This review summarizes the structural findings that formed the basis of modern antibody–Fc receptor biology and recent advances of shared Fc receptor recognition by innate pentraxins.
| Author | : William R Strohl |
| Publisher | : Elsevier |
| Total Pages | : 697 |
| Release | : 2012-10-16 |
| Genre | : Medical |
| ISBN | : 1908818093 |
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
