Therapeutic Modulation of the Complement System: Clinical Indications and Emerging Drug Leads

Therapeutic Modulation of the Complement System: Clinical Indications and Emerging Drug Leads PDF

Author: John D. Lambris

Publisher: Frontiers Media SA

Published: 2020-02-14

Total Pages: 185

ISBN-13: 2889634701

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The complement system is a multi-tasking gatekeeper of innate immunity thatintricately interacts with other key defense systems, such as the endothelial barrier,contact activation and coagulation systems, in maintaining tissue immunosurveillanceand homeostasis. Its rapid and forceful activation in the bloodstream not onlyensures the effective containment of microbial infections through potent cytolyticmechanisms, but also alerts the adaptive immune compartment to ensure the mountingof a proper humoral immune response against foreign antigens. However, there isa lurking ‘dark side’ that can lead complement astray, fueling a self-perpetuatingvicious cycle of inflammation, exuberant immune activation and irreversible tissueinjury that collectively exacerbate both acute and chronic pathologies. Indeed,complement dysregulation or excessive activation have been widely recognized askey pathogenic drivers in a wide spectrum of inflammatory or immune-mediateddiseases. Targeted modulation of the complement system at various points ofthe cascade has revealed promising therapeutic targets for ameliorating diseasescores in a number of conditions ranging from ocular, neurodegenerative andthromboinflammatory disorders, to cancer, periodontal diseases, chronic hemolyticanemias, ischemia-reperfusion organ injury, antibody-mediated transplant rejectionand hemodialysis-triggered inflammation. Elegant pre-clinical studies employing a diversified toolbox of highly specificcomplement inhibitors in rodent or primate models of disease have opened newavenues of therapeutic exploration by providing proof of concept for the therapeuticefficacy of complement modulation. At the same time, the clinical experience gainedduring this last decade with the sole complement-specific drug currently in the clinic,eculizumab, has rekindled the interest of biopharmaceutical companies in developingnew and potent complement therapeutics for complement-driven diseases. In this respect, the complement field is witnessing a new surge of clinical trialsthat are evaluating the safety, PK/PD profile and clinical efficacy of promising drugcandidates in a number of clinical conditions driven by complement imbalance orover-activation.

Complement Therapeutics

Complement Therapeutics PDF

Author: John D. Lambris

Publisher: Springer

Published: 2012-09-19

Total Pages: 320

ISBN-13: 9781461441199

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This book highlights progress and trends in the rapidly evolving field of complement-related drug discovery and spotlights examples of clinical applications. As an integral part of innate immunity and critical mediator in homeostatic and inflammatory processes, the human complement system has been identified as contributor to a large number of disorders including ocular, cardiovascular, metabolic, autoimmune, and inflammatory diseases as well as in ischemia/reperfusion injury, cancer and sepsis. In addition, complement is often involved in adverse immune reactions to biomaterials, cell and organ transplants or drug delivery systems. Although the complement cascade with its close to 50 extracellular protein targets has long been recognized as an attractive system for therapeutic modulation, the past few years have seen a particularly strong boost in interest. Fueled by novel research insight and the marketing of the first complement-targeted drugs, a plethora of highly creative treatment approaches and potent drug candidates have recently emerged and are currently evaluated in disease models and clinical trials. The chapters in this book cover a wide range of topics related to the development of complement therapeutics, ranging from the molecular and functional description of complement targets to the presentation of novel inhibitors, improved treatment strategies as well as examples of disease models and clinical applications. The broad and up-to-date overview on a highly versatile and dynamic field renders this book an indispensable source of information for researchers and clinicians dealing with therapeutic and disease-related aspects of the human complement system.

Complement Therapeutics

Complement Therapeutics PDF

Author: John D. Lambris

Publisher: Springer Science & Business Media

Published: 2012-09-19

Total Pages: 323

ISBN-13: 146144117X

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This book highlights progress and trends in the rapidly evolving field of complement-related drug discovery and spotlights examples of clinical applications. As an integral part of innate immunity and critical mediator in homeostatic and inflammatory processes, the human complement system has been identified as contributor to a large number of disorders including ocular, cardiovascular, metabolic, autoimmune, and inflammatory diseases as well as in ischemia/reperfusion injury, cancer and sepsis. In addition, complement is often involved in adverse immune reactions to biomaterials, cell and organ transplants or drug delivery systems. Although the complement cascade with its close to 50 extracellular protein targets has long been recognized as an attractive system for therapeutic modulation, the past few years have seen a particularly strong boost in interest. Fueled by novel research insight and the marketing of the first complement-targeted drugs, a plethora of highly creative treatment approaches and potent drug candidates have recently emerged and are currently evaluated in disease models and clinical trials. The chapters in this book cover a wide range of topics related to the development of complement therapeutics, ranging from the molecular and functional description of complement targets to the presentation of novel inhibitors, improved treatment strategies as well as examples of disease models and clinical applications. The broad and up-to-date overview on a highly versatile and dynamic field renders this book an indispensable source of information for researchers and clinicians dealing with therapeutic and disease-related aspects of the human complement system.

Therapeutic Interventions in the Complement System

Therapeutic Interventions in the Complement System PDF

Author: John D. Lambris

Publisher: Humana Press

Published: 2012-11-05

Total Pages: 260

ISBN-13: 9781468496116

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A team of expert investigators and clinical researchers comprehensively review complement's basic biology, its role in disease, methods to measure its activity, and strategies for its inhibition in patients. Each chapter focuses on a specific area of basic and applied complement biology, spelling out the activation pathways and complement receptors. Informative animal models are discussed in detail, including the relative values of each model and the important interspecies differences that can distort the interpretation of preclinical studies. The emphasis throughout is on the pros and cons of the therapeutic use of recombinant complement inhibitors in specific diseases. Cutting-edge and innovative, Therapeutic Interventions in the Complement System highlights for today's researcher and biotechnologist effective strategies of drug discovery and development that are producing valuable new complement inhibitors for the treatment of a wide variety of clinically important diseases.

Treating Infectious Diseases in a Microbial World

Treating Infectious Diseases in a Microbial World PDF

Author: National Research Council

Publisher: National Academies Press

Published: 2006-01-03

Total Pages: 102

ISBN-13: 0309180686

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Humans coexist with millions of harmless microorganisms, but emerging diseases, resistance to antibiotics, and the threat of bioterrorism are forcing scientists to look for new ways to confront the microbes that do pose a danger. This report identifies innovative approaches to the development of antimicrobial drugs and vaccines based on a greater understanding of how the human immune system interacts with both good and bad microbes. The report concludes that the development of a single superdrug to fight all infectious agents is unrealistic.

Complement Regulatory Proteins

Complement Regulatory Proteins PDF

Author: B. Paul Morgan

Publisher: Academic Press

Published: 1999-02-18

Total Pages: 382

ISBN-13: 9780080529561

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From small beginnings in the early 1970s, the study of complement regulatory proteins has grown in the last decade to the point where it dominates the complement field. This growth has been fueled by the discovery of new regulators, the cloning of old and new regulators, the discovery that many of the regulators are structurally and evolutionarily related to each other and the development of recombinant forms for use in therapy. There are now more proteins known to be involved in controlling the complement system than there are components of the system and the list continues to grow. The time is ripe for a comprehensive review of our current knowledge of these intriguing proteins. This book does just that. The first few chapters discuss the "nuts-and-bolts" of the complement regulators, describing their structures, functional roles and modes of action. The roles of the complement regulators in vivo are then described, focusing on the consequences of deficiency, roles in the reproductive system, interactions with pathogens and exploitation for therapy. The interesting developments in defining the complement regulators expressed in other species are also discussed. The book is written as a monograph, albeit by two people. The text is as readable as possible without compromising on scientific accuracy and completeness. The conversational style very evident in some sections is deliberate! Placing all references in a single bibliography at the end of the text further improves readability. The reader will go to the book to discover a specific fact but be persuaded to read more and derive pleasure from the process. The authors' enthusiasm for the subject comes over strongly in the text, and this enthusiasm proves infectious. Complement regulators--structure, functional roles and mode of action Comprehensive reviews of each of the individual regulators Roles of Complement regulators in vivo,in health and disease: Consequences of deficiency Roles in the reproductive system Interactions with pathogens Exploitation for therapy Complement regulators in other species

CDC Yellow Book 2018: Health Information for International Travel

CDC Yellow Book 2018: Health Information for International Travel PDF

Author: Centers for Disease Control and Prevention CDC

Publisher: Oxford University Press

Published: 2017-04-17

Total Pages: 672

ISBN-13: 0190628634

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THE ESSENTIAL WORK IN TRAVEL MEDICINE -- NOW COMPLETELY UPDATED FOR 2018 As unprecedented numbers of travelers cross international borders each day, the need for up-to-date, practical information about the health challenges posed by travel has never been greater. For both international travelers and the health professionals who care for them, the CDC Yellow Book 2018: Health Information for International Travel is the definitive guide to staying safe and healthy anywhere in the world. The fully revised and updated 2018 edition codifies the U.S. government's most current health guidelines and information for international travelers, including pretravel vaccine recommendations, destination-specific health advice, and easy-to-reference maps, tables, and charts. The 2018 Yellow Book also addresses the needs of specific types of travelers, with dedicated sections on: · Precautions for pregnant travelers, immunocompromised travelers, and travelers with disabilities · Special considerations for newly arrived adoptees, immigrants, and refugees · Practical tips for last-minute or resource-limited travelers · Advice for air crews, humanitarian workers, missionaries, and others who provide care and support overseas Authored by a team of the world's most esteemed travel medicine experts, the Yellow Book is an essential resource for travelers -- and the clinicians overseeing their care -- at home and abroad.

Pharmacology of Immunotherapeutic Drugs

Pharmacology of Immunotherapeutic Drugs PDF

Author: Clinton B. Mathias

Publisher: Springer Nature

Published: 2019-10-18

Total Pages: 399

ISBN-13: 3030199223

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Medicine has entered a golden age in which therapeutic agents are becoming widely available due to advances in basic science and technology. As such, many drugs have been developed that target inflammatory processes and/or the immune system. This book is intended for health professionals examining the modulation of inflammation by immunotherapeutic drugs. The immune system fills the primordial role of host defense and resistance to infections with pathogenic microorganisms. Several hematopoietic-derived cells constituting the innate and adaptive immune systems cooperate to provide barriers for microbial colonization and/or promote pathogen destruction within the host. Conversely, many immune cells are also involved in the pathogenesis and propagation of chronic inflammatory diseases. The beginning of this book details various components of the immune system including the cell types, lymphoid tissues, soluble cytokines and surface molecules that are essential for host defense. Breakdowns in immune tolerance, or dysregulated immune responses to antigens derived from self tissues or innocuous sources, can lead to the development of autoimmunity or chronic inflammatory diseases. Pathophysiologic roles for the immune system are detailed in corresponding chapters on autoimmunity, epithelial surfaces (lungs, skin, intestine), and transplantation, with special emphasis placed on immunotherapeutic drug targets. The last section of the book focuses on treatments that stimulate our immune system to specifically target and fight infectious diseases and cancer. In each chapter, the medications used to treat various diseases/conditions in terms of their mechanism of action and other pharmacologic properties are detailed. Chapters begin with a table showing drug names and classifications. The importance of basic science and clinical trials cannot be understated in the context of drug development. As such, the discovery of certain medications that had a lasting impact in medicine and pharmacy are highlighted in chapter subsections named “Bench to Bedside.” Several clinical applications of immunotherapeutic drugs are described within end-of -chapter case studies including practice questions. The Pharmacology of Immunotherapeutic Drugs is a reference for immunologists and clinicians (medical doctors, pharmacists, nurses) examining the modulation of inflammatory processes by a variety of medications targeting the cells and mediators of our immune system.​

Immunopharmacology

Immunopharmacology PDF

Author: Manzoor M. Khan

Publisher: Springer Science & Business Media

Published: 2008-12-19

Total Pages: 275

ISBN-13: 0387779760

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During the past decades, with the introduction of the recombinant DNA, hybridoma and transgenic technologies there has been an exponential evolution in understanding the pathogenesis, diagnosis and treatment of a large number of human diseases. The technologies are evident with the development of cytokines and monoclonal antibodies as therapeutic agents and the techniques used in gene therapy. Immunopharmacology is that area of biomedical sciences where immunology, pharmacology and pathology overlap. It concerns the pharmacological approach to the immune response in physiological as well as pathological events. This goals and objectives of this textbook are to emphasize the developments in immunology and pharmacology as they relate to the modulation of immune response. The information includes the pharmacology of cytokines, monoclonal antibodies, mechanism of action of immune-suppressive agents and their relevance in tissue transplantation, therapeutic strategies for the treatment of AIDS and the techniques employed in gene therapy. The book is intended for health care professional students and graduate students in pharmacology and immunology.

Concepts and Principles of Pharmacology

Concepts and Principles of Pharmacology PDF

Author: James E. Barrett

Publisher: Springer Nature

Published: 2019-12-24

Total Pages: 466

ISBN-13: 3030353621

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Celebrating 100 years of HEP, this volume will discuss key pharmacological discoveries and concepts of the past 100 years. These discoveries have dramatically changed the medical treatment paradigms of many diseases and these concepts have and will continue to shape discovery of new medicinies. Newly evolving technologies will similarly be discussed as they will shape the future of the pharmacology and, accordingly, medical therapy.