Antibody-Drug Conjugates. Fundamentals, Drug Development, and Clinical Outcomes to Target Cancer

Description

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 efficacyof 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

Contents

Preface
Olivier and Hurvitz

Introduction: Historical perspective: What makes ADCs revolutionary
Kim Blackwell and Lynn Howie

Part I: What is an ADC

Chapter 1: Typical Antibody-Drug Conjugates
John Lambert

Part II: Engineering, Manufacturing, and Optimizing ADCs

Chapter 2: Selecting Optimal ADC Targets Using Indication-Dependent or Indication-Independent Approaches
Robert Hollingsworth and Jay Harper

Chapter 3: Antibody Drug Conjugates: An overview of the CMC and characterization process
Janet Wolfe and Phillip Ross

Chapter 4: Linker and Conjugation Technology and Improvements
Riley Ennis and Sourav Sinha

Chapter 5: Formulation and Stability
Kouhei Tsumoto, Anthony Young and Satoshi Ohtake

Chapter 6: QC Assay Development
Xiao-Hong Chen and Mate Tolnay

Chapter 7: Occupational Health and Safety Aspects of ADCs and Their Toxic Payloads
Robert Sussman and John Farris

Part III: Nonclinical Approaches

Chapter 8: Bioanalytical Strategies Enabling Successful ADC Translation
Xiaogang Han, Lindsay King and Steve Hansel

Chapter 9: Nonclinical Pharmacology and Mechanistic Modeling of Antibody–Drug Conjugates in Support of Human Clinical Trials
Brian J. Schmidt, Chin Pan, Heather E. Vezina, Huadong Sun, Douglas D. Leipold and Manish Gupta

Chapter 10: Pharmacokinetics of Antibody-Drug Conjugates
Amrita Kamath

Chapter 11: Path to Market Approval:  Regulatory Perspective of ADC Nonclinical Safety Assessments
Stacey Ricci and Natalie Simpson

Part IV: Clinical Development and Current Status of ADCs

Chapter 12: Antibody–Drug Conjugates: Clinical Strategies and Applications
Heather E. Vezina, Lucy Lee, Brian J. Schmidt, Manish Gupta

Chapter 13: Antibody-Drug Conjugates (ADCs) in Clinical Development
Patricia LoRusso and Joseph McLaughlin

Chapter 14: ADCs approved for use: Trastuzumab emtansine (Kadcyla®, T-DM1) in patients with previously treated HER2-positive metastatic breast cancer
Gail Lewis Phillips, Sanne de Hass, Sandhya Girish and Ellie Guardino

Chapter 15: ADCs approved for use: Brentuximab Vedotin
Sven DeVos and Monica Mead

Chapter 16: Radioimmunotherapy
Jeffrey Wong and Savita Dandapani

Part V: Future Perspectives in ADC Development

Chapter 17: Radiolabeled Antibody-based Imaging in Clinical Oncology
Bart Hendriks and Daniel Gaddy

Chapter 18: Next Generation ADC Technologies
William C Olson and Amy Q. Han

Index

Author Information

Kenneth J. Olivier, Jr., PhD, is Head of Toxicology, Discovery Regulatory, Bioanalytical Assay Development, Pharmacokinetics and Discovery Project Management at MerrimackPharmaceuticals 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.