Antibody-drug conjugates (ADCs) stand at the verge of a transformation. Scores of clinical programs have yielded only a few regulatory approvals, but a wave of technological innovation now empowers us to overcome past technical challenges. This volume focuses on the next generation of ADCs and the innovations that will enable them. The book inspires the future by integrating the field's history with novel strategies and cutting-edge technologies. While the book primarily addresses ADCs for solid tumors, the last chapter explores the emerging interest in using ADCs to treat other diseases. The therapeutic rationale of ADCs is strong: to direct small molecules to the desired site of action (and away from normal tissues) by conjugation to antibodies or other targeting moieties. However, the combination of small and large molecules imposes deep complexity to lead optimization, pharmacokinetics, toxicology, analytics and manufacturing. The field has made significant advances in all of these areas by improving target selection, ADC design, manufacturing methods and clinical strategies. These innovations will inspire and educate scientists who are designing next-generation ADCs with the potential to transform the lives of patients.

Autorentext

Marc Damelin is Senior Director, Biology at Mersana Therapeutics in Cambridge, Massachusetts. His group is responsible for the discovery of therapeutic ADCs enabled by Mersana's proprietary linker-payload-scaffold technologies. Prior, Marc spent 10 years at Pfizer Inc. in the Oncology Research Unit, where he led ADC discovery teams and ultimately oversaw the ADC portfolio. He received his Ph.D. in Biophysics from Harvard University and conducted postdoctoral research at Columbia University Medical School as a Fellow of the Damon Runyon Cancer Research Foundation.

Klappentext

Antibody-drug conjugates (ADCs) stand at the verge of a transformation. Scores of clinical programs have yielded only a few regulatory approvals, but a wave of technological innovation now empowers us to overcome past technical challenges. This volume focuses on the next generation of ADCs and the innovations that will enable them. The book inspires the future by integrating the field's history with novel strategies and cutting-edge technologies. While the book primarily addresses ADCs for solid tumors, the last chapter explores the emerging interest in using ADCs to treat other diseases. The therapeutic rationale of ADCs is strong: to direct small molecules to the desired site of action (and away from normal tissues) by conjugation to antibodies or other targeting moieties. However, the combination of small and large molecules imposes deep complexity to lead optimization, pharmacokinetics, toxicology, analytics and manufacturing. The field has made significant advances in all of these areas by improving target selection, ADC design, manufacturing methods and clinical strategies. These innovations will inspire and educate scientists who are designing next-generation ADCs with the potential to transform the lives of patients.

Inhalt

Chapter 1. Introduction: Motivations for Next-Generation ADCs -Marc Damelin

Chapter 2. Combining ADCs with Immuno-oncology Agents -- Philipp Müller, Jonathan Rios-Doria, Jay Harper and Anthony Cao

Chapter 3. Improving the Safety Profile of ADCs -- MagaliGuffroy, HadiFalahatpisheh and Martin Finkelstein Chapter 4. Utility of PK-PD Modeling and Simulation to Improve Decision Making for Antibody-Drug Conjugate Development -- Aman P. Singh and Dhaval K. Shah

Chapter 5.Regulatory Considerations and Companion Diagnostics Elizabeth VanAlphen and Omar Perez

Chapter 6. ADC Process Development and Manufacturing Olivier Marcq

Chapter 7. HER2-Targeted ADCs: At the forefront of ADC technology development Kevin J. Hamblett Chapter 8. Next generation payloads for ADCs L. Nathan Tumey

Chapter 9.Delivering more payload: High DAR ADCs - Natalya Bodyak and Alexander V.Yurkovetskiy

Chapter 10.Site-Specific Antibody Drug Conjugates Feng Tian, Dowdy Jackson and Yun Bai

Chapter 11. Bispecific and Biparatopic Antibody-Drug Conjugates -- Frank Comer, Changshou Gao and Steve Coats

Chapter 12. Targeting drug conjugates to the tumor microenvironment: Probody Drug Conjugates -- Jack Lin and Jason Sagert

Chapter 13.Antibody-Drug Conjugates: Targeting the Tumor Microenvironment Alberto Dal Corso, SamueleCazzamalli and Dario Neri

Chapter 14. Next Horizons: ADCs Beyond Oncology -- Shan Yu, Andrew Lim and Matthew S. Tremblay