Antibody-Drug Conjugates: The 21st Century Magic Bullets for Cancer

ISBN-13: 9783319376691 / Angielski / Miękka / 2016 / 252 str.

Jeffrey Wang; Wei-Chiang Shen; Jennica L. Zaro

Opis

Case studies are presented for the three ADCs that have received FDA approval: gemtuzumab ozogamicin (Mylotarg (R)), Brentuximab vedotin (Adcetris (R)), and ado-trastuzumab emtansine (Kadcyla (R)), as well as an ADC in late-stage clinical trials, glembatumumab vedotin (CDX-011).

Spis treści

.- I Introduction

.- 1 Antibody-Drug Conjugates: A Historical Review (Wei-Chiang Shen)

.- II The ADC Construct

.- 2 Payloads of Antibody-Drug Conjugates (Chalet Tan)

.- 3 Selecting an Optimal Antibody for Antibody-Drug Conjugate Therapy (Michael Ritchie, Laird Bloom, Gregory Carven, and Puja Sapra)

.- 4 Linker Design for Antibody-Drug Conjugates (E. Erica Hong and Ravi Chari)

.- III Development Issues

.- 5 Formulation Development for Antibody-Drug Conjugates (Junyan A. Ji, Jun Liu, Y. John Wang)

.- 6 Bioanalytical Assay for Characterization of Antibody Drug Conjugates (Chen Xie and Zhijun Wang)

.- 7 Pharmacokinetics/Pharmacodynamics and Disposition of Antibody-Drug Conjugates (Siddharth Sukumaran and Kedan Lin)

.- 8 Regulatory Considerations (Karen J. Cha)

.- IV Landscape, IP and Pharmacoeconomics

.- 9 Major ADC Companies, Current Clinical Trials, Recent Patents Issued and Patent Applications, and Cost Analysis of Drug Therapy (Jeffrey Wang and Jonathan H. Watanabe)

.- V Case Studies

.- 10 Mylotarg: Revisiting its Clinical Potential Post-Withdrawal (Jennica L. Zaro)

.- 11 ADCETRIS: A Regulatory Case Study of a New Generation Antibody Drug Conjugate (Bruce W. Hart Jr.)

.- 12 Ado-Trastuzumab Emtansine (Yun Luo, Jérôme J. Lacroix and Sunil Prabhu)

.- 13 The Antibody-Drug Conjugate Glembatumumab Vedotin (CDX-011) and its Use in Treatment of Breast Cancer (Nancy Chan and Linda T. Vahdat)

.- VI From Today to Tomorrow

.- 14 Summary and Future Directions (Jennica L. Zaro, Jeffery Wang and Wei-Chiang Shen).

O autorze

Dr. Jeffrey Wang received his PhD in pharmaceutical sciences from the University of Southern California in Los Angeles.  Dr. Wang’s research focuses on the application of principles of pharmacokinetics and drug metabolism in drug discovery and delivery, particularly in anti-cancer drug discovery and peptide and protein drug delivery.  He has published more than 100 peer-reviewed articles, book chapters and meeting abstracts and is the co-inventor of several U.S. and international patents.  Dr. Wang is currently Associate Professor of Pharmaceutical Sciences and Director of Graduate Education at the College of Pharmacy, Western University of Health Sciences, Pomona, California.

Dr. Wei-Chiang Shen is John A. Biles Professor in Pharmaceutical Sciences at the University of Southern California’s School of Pharmacy in Los Angeles.  Dr. Shen received his PhD in bio-organic chemistry from Boston University, Massachusetts.  He has many years of experience on the conjugation of drug to macromolecules, including poly (amino acids), transferrin and antibodies.  His current focus of research is on recombinant fusion proteins and cell-penetrating peptides.  Dr. Shen has published about 150 papers, mostly in the area of drug delivery.  He is an inventor or co-inventor of 16 issued U.S. patents and a Fellow of the American Association of Pharmaceutical Scientists and the American Association for the Advancement of Science.

Dr. Jennica L. Zaro is a Research Assistant Professor at the School of Pharmacy, University of Southern California, Los Angeles.  Her main research projects are focused on targeted delivery of peptide and protein drugs and on recombinant bifunctional fusion proteins as therapeutics.  Dr. Zaro is also the Core Director of the Translational Research Laboratory.  Prior to joining the university, Dr. Zaro received her PhD in pharmaceutical sciences from the University of Southern California, where she focused on the design and characterization of peptide carriers for protein drugs.  In addition, she has held several roles in the pharmaceutical industry, where she developed formulations for aerosol products and designed and validated analytical methods for protein drugs.

Blurb

This authoritative volume provides a holistic picture of antibody-drug conjugates (ADCs). Fourteen comprehensive chapters are divided into six sections including an introduction to ADCs, the ADC construct, development issues, landscape, IP and pharmacoeconomics, case studies, and the future of the field. The book examines everything from the selection of the antibody, the drug, and the linker to a discussion of developmental issues such as formulations, bio-analysis, pharmacokinetic-pharmacodynamic relationships, and toxicological and regulatory challenges. It also explores pharmacoecomonics and intellectual properties, including recently issued patents and the cost analysis of drug therapy. Case studies are presented for the three ADCs that have received FDA approval: gemtuzumab ozogamicin (Mylotarg®), Brentuximab vedotin (Adcetris®), and ado-trastuzumab emtansine (Kadcyla®), as well as an ADC in late-stage clinical trials, glembatumumab vedotin (CDX-011). Finally, the volume presents a perspective by the editors on the future directions of ADC development and clinical applications. Antibody-Drug Conjugates is a practical and systematic resource for scientists, professors, and students interested in expanding their knowledge of cutting-edge research in this exciting field.