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Informationen zum Autor Kenneth J. Olivier, Jr., PhD, is Head of Toxicology, Discovery Regulatory, Bioanalytical Assay Development, Pharmacokinetics and Discovery Project Management at Merrimack Pharmaceuticals and has over 13 years' experience in the biotechnology and pharmaceutical industries. Sara A. Hurvitz, MD, is an Associate Professor of Medicine at the University of California, Los Angeles (UCLA); Co-Director of the Santa Monica-UCLA Outpatient Oncology Practice; Medical Director of the Clinical Research Unit of the Jonsson Comprehensive Cancer Center of UCLA; and Director of the Breast Oncology Program, Division of Hematology-Oncology, at UCLA. Klappentext Antibody-drug conjugates (ADCs) are a type of targeted therapy, used most notably for cancer, and consist of an antibody (or antibody fragment) linked to a payload drug which is often cytotoxic. Because of the targeting, the side effects should be lower and give a wider therapeutic window. By combining the unique targeting of antibodies with the cancer-killing ability of cytotoxic drugs, ADCs allow sensitive discrimination between healthy and diseased tissue - leading to widespread enthusiasm in the oncology drug development community. Providing practical and proven solutions for ADC drug discovery success in oncology, Antibody-Drug Conjugates: Fundamentals, Drug Development, and Clinical Outcomes to Target Cancer helps readers improve the drug safety and therapeutic efficacy of ADCs to kill targeted tumor cells. Featuring contributions from highly-regarded experts on the frontlines of ADC research and development, the book covers the basics, chemistry and manufacturing (CMC) controls, nonclinical pharmacology and toxicology, clinical outcomes and regulatory approval strategies, and case studies from oncology drug discovery. Readers benefit through gaining an improved understanding of ADC fundamentals, strategies for targeted and tailored drug release, computational modelling practices, and insights into optimizing and assessing nonclinical studies and regulatory strategies. In addition, the chapters offer discussion on the conduct and design of oncology clinical trials, using ADCs to image tumors and guide clinical protocol development, and therapeutic regimens. Considering how expansive the field is and the potential benefit to researchers, clinicians, and - ultimately -patients, this comprehensive book with the newest cutting edge information offers a critical resource and reference for the growth of oncology drug development. Zusammenfassung Providing practical and proven solutions for antibody-drug conjugate (ADC) drug discovery success in oncology! this book helps readers improve the drug safety and therapeutic efficacy of ADCs to kill targeted tumor cells. Inhaltsverzeichnis List of Contributors xvii Preface xxi Historical Perspective: What Makes Antibody-Drug Conjugates Revolutionary? xxiii Part I What is an Antibody-Drug Conjugate 1 1 Typical Antibody-Drug Conjugates 3 John M. Lambert 1.1 Introduction 3 1.1.1 A Simple Concept 3 1.1.2 Turning Antibodies into Potent Anticancer Compounds 4 1.1.3 What is a Typical ADC and How Does it Act? 4 1.1.4 Simple Concept, but Not So Simple to Execute 5 1.2 The Building Blocks of a Typical ADC 6 1.2.1 The Antibody 6 1.2.1.1 Antibody Isotype in ADCs 7 1.2.1.2 Functional Activity of the Antibody Moiety in ADCs 8 1.2.2 The Payload 9 1.2.2.1 DNA-Targeting Payloads 11 1.2.2.2 Payloads Targeting Tubulin 11 1.2.3 Linker Chemistries 12 1.3 Building an ADC Molecule 13 1.3.1 Conjugation of Payloads to Antibodies at Lysine Residues 13 1.3.2 Conjugation of Payloads to Antibodies at Cysteine Residues 17 1.4 Attributes of a Typical ADC 19 1.4.1 Structur...
