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Book Cover
Author Olivier, Kenneth J

Title Antibody-Drug Conjugates : Fundamentals, Drug Development, and Clinical Outcomes to Target Cancer
Published New York : John Wiley & Sons, Incorporated, 2016


Description 1 online resource (566 pages)
Contents Cover; Title Page; Copyright; Contents; List of Contributors; Preface; Historical Perspective: What Makes Antibody-Drug Conjugates Revolutionary?; Introduction; Early Work in Monoclonal Antibody Development: Ehrlich's Magic Bullets; Use of Monoclonal Antibodies to Identify and Treat Cancer; Linking Monoclonal Antibodies with Cytotoxic Agents; Antibody-Drug Conjugates in the Clinic; Why ADCs Are Revolutionary?; References; Part I 1 What is an Antibody-Drug Conjugate; Chapter 1 Typical Antibody-Drug Conjugates; 1.1 Introduction; 1.1.1 A Simple Concept
1.1.2 Turning Antibodies into Potent Anticancer Compounds1.1.3 What is a Typical ADC and How Does it Act?; 1.1.4 Simple Concept, but Not So Simple to Execute; 1.2 The Building Blocks of a Typical ADC; 1.2.1 The Antibody; Antibody Isotype in ADCs; Functional Activity of the Antibody Moiety in ADCs; 1.2.2 The Payload; DNA-Targeting Payloads; Payloads Targeting Tubulin; 1.2.3 Linker Chemistries; 1.3 Building an ADC Molecule; 1.3.1 Conjugation of Payloads to Antibodies at Lysine Residues; 1.3.2 Conjugation of Payloads to Antibodies at Cysteine Residues
1.4 Attributes of a Typical ADC1.4.1 Structural Attributes of a Typical ADC; 1.4.2 Functional Characteristics of a Typical ADC; In Vitro Properties; In Vivo Efficacy; Pharmacokinetics of ADCs; 1.5 Summary; Acknowledgment; References; Part II Engineering, Manufacturing, and Optimizing Antibody-Drug Conjugates; Chapter 2 Selecting Optimal Antibody-Drug Conjugate Targets Using Indication-Dependent or Indication-Independent Approaches; 2.1 Characteristics of an Optimal ADC Target; 2.2 Indication-Dependent ADC Target Selection
2.3 Indication-Independent ADC Target Selection2.4 Concluding Remarks and Future Directions; Acknowledgments; References; Chapter 3 Antibody-Drug Conjugates: An Overview of the CMC and Characterization Process; 3.1 Introduction; 3.2 ADC Manufacturing Process; 3.2.1 Conjugation; 3.2.2 Conjugation -- Next-Generation Chemistry; Conjugation -- Novel Payloads; Conjugation -- Linker Design; 3.2.3 mAb Engineering; 3.2.4 Purification; 3.2.5 Formulation; 3.3 Characterization; 3.3.1 Quality and Stability Testing; 3.3.2 Biochemical and Microbiological Testing
3.3.3 Extended Characterization3.4 Comparability; 3.5 Concluding Remarks; References; Chapter 4 Linker and Conjugation Technology; and Improvements; 4.1 Overview; 4.2 Noncleavable; 4.3 Cleavable Linkers and Self-Immolative Groups; 4.4 Differences in Therapeutic Window of Cleavable and Noncleavable Linkers; 4.5 Improving Therapeutic Window with Next-Generation Linker Technologies; 4.6 Site-Specific Conjugation, Homogeneous Drug Species, and Therapeutic Window; 4.7 Influence of Linkers on Pharmacokinetics and ADME; 4.8 PEG Linkers to Optimize Clearance, Solubility, and Potency
Summary 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. - Discusses the basics, drug delivery strategies, pharmacology and toxicology, and regulatory approval strategies- Covers the conduct and design of oncology clinical trials and the use of ADCs for tumor imaging- Includes case studies of ADCs in oncology drug development- Features contributions from highly-regarded experts on the frontlines of ADC research and development
Notes 4.9 Linkers to Optimize for Drug Resistance
Print version record
Subject Antibody-toxin conjugates.
Monoclonal antibodies.
Antineoplastic agents.
Tumors -- Treatment
Antimitotic agents.
Antibodies, Monoclonal
Antimitotic Agents
Antineoplastic Agents
MEDICAL -- Pharmacology.
Antimitotic agents.
Antibody-toxin conjugates.
Antineoplastic agents.
Monoclonal antibodies.
Tumors -- Treatment.
Form Electronic book
Author Hurvitz, Sara A
ISBN 9781119060802