Chemical Linkers in Antibody-Drug Conjugates (ADCs)


Book Description

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.




Chemical Linkers in Antibody–Drug Conjugates (ADCs)


Book Description

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.




Antibody-Drug Conjugates


Book 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 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




Innovations for Next-Generation Antibody-Drug Conjugates


Book Description

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.




Antibody-Drug Conjugates


Book Description

Antibody-drug conjugates (ADCs) represent a promising therapeutic approach for cancer patients by combining the antigen-targeting specificity of monoclonal antibodies (mAbs) with the cytotoxic potency of chemotherapeutic drugs. In Antibody-Drug Conjugates, expert researchers provide detailed protocols for many of the key ADC techniques necessary for working in the field. These chapters and methodologies are aimed at the key tasks necessary to identify a suitable target, properly design the mAb, the linker and the payload, as well as to conjugate them in a reproducible and scalable fashion. Written in the highly successful Methods in Molecular BiologyTM format, these detailed chapters include the kind of practical implementation advice that guarantees quality results. Authoritative and timely, Antibody-Drug Conjugates aims to further drive ADC development and thus help toward improving cancer treatments of the future.




Antibody Drug Discovery


Book Description

Antibody-based therapeutics are a central driver of the success of biopharmaceuticals. The discovery technology of this field is isolated to a limited number of centers of excellence in industry and academia. The objective of this volume is to provide a series of guides to those evaluating and preparing to enter particular areas within the field. Each chapter is written with a historical perspective that sets into context the significance of the key developments, and with the provision of “points to consider” for the reader as a value-added feature of the volume. All contributors are experts in their fields and have played pivotal roles in the creation of the technology.




Cytotoxic Payloads for Antibody–Drug Conjugates


Book Description

Antibody–drug conjugates (ADCs) represent one of the most promising and exciting areas of anticancer drug discovery. Five ADCs are now approved in the US and EU [i.e., ado-trastuzumab emtansine (Kadcyla™), brentuximab vedotin (Adcetris™), inotuzumab ozogamicin (Besponsa™), gemtuzumab ozogamicin (Mylotarg™) and moxetumomab pasudotox-tdfk (Lumoxiti®)] and over 70 others are in various stages of clinical development, with impressive interim results being reported for many. The technology is based on the concept of delivering a cytotoxic payload selectively to cancer cells by attaching it to an antibody targeted to antigens on the cell surfaces. This approach has several advantages including the ability to select patients as likely responders based on the presence of antigen on the surface of their cancer cells and a wider therapeutic index, given that ADC targeting enables a more efficient delivery of cytotoxic agents to cancer cells than can be achieved by conventional chemotherapy, thus minimising systemic toxicity. Although there are many examples of antibodies that have been developed for this purpose, along with numerous linker technologies used to attach the cytotoxic agent to the antibody, there is presently a relatively small number of payload molecules in clinical use. The purpose of this book is to describe the variety of payloads used to date, along with a discussion of their advantages and disadvantages and to provide information on novel payloads at the research stage that may be used clinically in the future.




Next Generation Antibody Drug Conjugates (ADCs) and Immunotoxins


Book Description

This book describes the newest developments in antibody drug conjugates and immunotoxins, paving their way to clinical application. Lessons learned from the current state of the art are used to further improve our understanding of their mechanisms of action and off target activities. The book introduces scientists to all of the prerequisites that must be properly addressed, including identification of the right target, specific traits of target binding antibodies, proper selection of the toxic payload, internalization induced by binding, and next generation conjugation and linker technologies. These knowledge-based, revolutionary new drug principles will form the cornerstone of the future standard of care and will lead to major advances in application, as well as improved quality of life and patient survival rates. This book will be of interest to biotech companies and researchers working in the fields of immunology, pharmacology, and oncology.




Biotherapeutics


Book Description

This book illustrates the successful partnership of chemistry and biology to advance successful biotherapeutic modalities. Molecular design to create function is common to both chemical and molecular biology, and this text highlights recent developments from these disciplines that have delivered drugs, clinical candidates or significantly advanced biotherapeutic approaches. Biotherapeutics are often considered to be beyond the reach of the medicinal chemist, but this book demonstrates that chemistry has an essential role in the future success of this area, by explaining and describing the chemical biology technologies that underpin specific therapeutic advances and demonstrating the unique value of molecular design and understanding. Covering topics such as selective protein modification, immunopharmacotherapy, chemically programmed vaccinations, nanobodies and antibodies, this book provides essential reading for medicinal and pharmaceutical chemists working in both industry and academia.




Antibody-Drug Conjugates


Book Description

This volume looks at key methodologies that are commonly used across antibody drug conjugates (ADCs) programs. The chapters in this book cover topics such as conjugations to endogenous cysteine residues; click chemistry conjugations; antibody conjugations via glycosyl remodeling; analysis of ADCs by native mass spectrometry; characterization of ADCs by capillary electrophoresis; LC/MS methods for studying lysosomal ADC catabolism; and determination of ADC concentration by ligand-binding assays. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Cutting-edge and practical, Antibody-Drug Conjugates: Methods and Protocols is a valuable resource that aims to lower the "activation barrier" when undertaking a new discipline, and provides a "toolbox" for the next generation of ADC scientists.