Chemical Linkers in Antibody-Drug Conjugates (ADCs)

by Floris van Delft (Editor), John M Lambert (Editor)

Overview

The covalent conjugation of potent cytotoxic agents to monoclonal antibodies, known as antibody—drug conjugates (ADCs) is a powerful approach in the field of targeted treatment of cancer. Clearly, both monoclonal antibody and cytotoxic payload are crucial elements in determining the clinical value of an ADC and have receive ample attention. However, the structural element connecting the two –the chemical linker– also plays an essential role in mode—of—action, efficacy, pharmacokinetics and safety profile of an ADC, but is often underappreciated in considerations of ADC design.
Chemical Linkers in Antibody–Drug Conjugates aims to shine a detailed light on the various key attributes of chemical linkers in ADCs, for drug—to—antibody ratio, for stability, for release mechanism of payload, for pharmacokinetics, for stability determination, and for efficacy and safety. Ideal for postgraduate students and active researchers in drug discovery and development, this book provides a comprehensive description of linkers used in ADCs (clinical and late preclinical), insight into key quality attributes of linkers for ADCs, and aids the reader in understanding the role of linker chemistry and designing new ADCs.

Product Details

ISBN-13:	9781839162633
Publisher:	RSC
Publication date:	12/22/2021
Series:	Drug Discovery Series , #81
Pages:	476
Product dimensions:	6.15(w) x 9.20(h) x (d)

Table of Contents

Introduction to Antibody–Drug Conjugates;
Antibody Conjugation Technologies;
Linker Design and Impact on ADC Properties;
Non—cleavable Linkers: Permanently Linked, for Better or for Worse;
Protease—sensitive Linkers;
Acid—labile Linkers;
ADC Linkers Strategies for the Release of Alcohol—containing Payloads;
Click—cleavable ADC Linkers;
The Use of Uniform PEG Compounds in the Design of ADCs;
Enhancing the Polarity of the Linker—drug in ADCs;
Trastuzumab Deruxtecan Targeting HER2—expressing Cancers with a DXd—ADC System Consisting of a Novel Protease—sensitive Linker and DNA Topoisomerase I Inhibitor with a Hydroxyl Group