Chemical Linkers in Antibody-Drug Conjugates (ADCs) PDF Download

Author: Floris van Delft
Publisher: Royal Society of Chemistry
ISBN: 1839162635
Category : Medical
Languages : en
Pages : 477

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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.

Author: Kenneth J. Olivier, Jr.
Publisher: John Wiley & Sons
ISBN: 1119060842
Category : Medical
Languages : en
Pages : 567

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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

Author: Marc Damelin
Publisher: Springer
ISBN: 3319781545
Category : Medical
Languages : en
Pages : 358

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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.

Author: Laurent Ducry
Publisher: Humana
ISBN: 9781493960262
Category : Medical
Languages : en
Pages : 0

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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.

Author: David E Thurston
Publisher: Royal Society of Chemistry
ISBN: 1788018451
Category : Medical
Languages : en
Pages : 502

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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 (KadcylaTM), brentuximab vedotin (AdcetrisTM), inotuzumab ozogamicin (BesponsaTM), gemtuzumab ozogamicin (MylotargTM) 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.

Author: Ulf Grawunder
Publisher: Springer
ISBN: 3319468774
Category : Medical
Languages : en
Pages : 191

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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.

Author: Martyna Pawlikowska
Publisher:
ISBN:
Category : Antibody-drug conjugates
Languages : en
Pages : 164

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Book Description
Antibody Drug Conjugates (ADC's) are an emerging class of therapeutics that combine the targeting capability of a monoclonal antibody with the efficacy of a small molecule drug attached by a chemical linker. The two most common conjugation chemistries for attaching the linker-drug to the antibody are maleimide-to-hinge-region cysteines or activated ester-to-surface lysines. ... We assessed the rate of maleimide hydrolysis, aggregation of ADC's, and the efficacy of ADC's in various bioassays. Our results indicated that addition of the basic group to the MP linker and hydrolysis at pH9 with arginine is the optimal linker to move forward with in ADC development.

Author: Lyn Jones
Publisher: Royal Society of Chemistry
ISBN: 1849737150
Category : Science
Languages : en
Pages : 331

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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.

Author:
Publisher: Academic Press
ISBN: 0080921639
Category : Science
Languages : en
Pages : 334

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Book Description
By combining the tools of organic chemistry with those of physical biochemistry and cell biology, Non-Natural Amino Acids aims to provide fundamental insights into how proteins work within the context of complex biological systems of biomedical interest. The critically acclaimed laboratory standard for 40 years, Methods in Enzymology is one of the most highly respected publications in the field of biochemistry. Since 1955, each volume has been eagerly awaited, frequently consulted, and praised by researchers and reviewers alike. With more than 400 volumes published, each Methods in Enzymology volume presents material that is relevant in today's labs -- truly an essential publication for researchers in all fields of life sciences. Demonstrates how the tools and principles of chemistry combined with the molecules and processes of living cells can be combined to create molecules with new properties and functions found neither in nature nor in the test tube Presents new insights into the molecular mechanisms of complex biological and chemical systems that can be gained by studying the structure and function of non-natural molecules Provides a "one-stop shop" for tried and tested essential techniques, eliminating the need to wade through untested or unreliable methods

Author: David E Thurston
Publisher: Royal Society of Chemistry
ISBN: 1788010779
Category : Medical
Languages : en
Pages : 502

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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.