Cytotoxic Payloads for Antibody – Drug Conjugates
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.
Cytotoxic Payloads for Antibody – Drug Conjugates, The Royal Society of Chemistry, 2019.
Download citation file:
Digital access
Print format
Table of contents
-
CHAPTER 1: Introduction to Antibody–Drug Conjugates (ADCs)p1-30ByIlona Pysz;Ilona PyszFemtogenix Ltd, Lawes Open Innovation Hub, Rothamsted Research, West CommonAL5 2JQHarpendenHertfordshireUKdavid.thurston@kcl.ac.ukKing's College London, Institute of Pharmaceutical Science, School of Cancer & Pharmaceutical Sciences, Faculty of Life Sciences & Medicine, Franklin–Wilkins Building150 Stamford StreetSE1 9NHLondonUKSearch for other works by this author on:Paul J. M. Jackson;Paul J. M. JacksonKing's College London, Institute of Pharmaceutical Science, School of Cancer & Pharmaceutical Sciences, Faculty of Life Sciences & Medicine, Franklin–Wilkins Building150 Stamford StreetSE1 9NHLondonUKSearch for other works by this author on:David E. ThurstonDavid E. ThurstonFemtogenix Ltd, Lawes Open Innovation Hub, Rothamsted Research, West CommonAL5 2JQHarpendenHertfordshireUKdavid.thurston@kcl.ac.ukKing's College London, Institute of Pharmaceutical Science, School of Cancer & Pharmaceutical Sciences, Faculty of Life Sciences & Medicine, Franklin–Wilkins Building150 Stamford StreetSE1 9NHLondonUKSearch for other works by this author on:
-
CHAPTER 2: Design Factors Important for Antibody–Drug Conjugate (ADC) Payloadsp31-56ByJohn M. LambertJohn M. LambertSearch for other works by this author on:
-
CHAPTER 3: Use of Molecular Modelling Techniques in Antibody–Drug Conjugate (ADC) Payload Discovery and Developmentp57-72ByPaul J. M. Jackson;Paul J. M. JacksonFemtogenix Ltd, Lawes Open Innovation Hub, Rothamsted Research, West CommonHarpendenHertfordshireAL5 2JQUKpaul.jackson@femtogenix.comSearch for other works by this author on:David E. ThurstonDavid E. ThurstonFemtogenix Ltd, Lawes Open Innovation Hub, Rothamsted Research, West CommonHarpendenHertfordshireAL5 2JQUKpaul.jackson@femtogenix.comKing's College London, Institute of Pharmaceutical Science, School of Cancer & Pharmaceutical Sciences, Faculty of Life Sciences & Medicine, Franklin–Wilkins Building150 Stamford StreetSE1 9NHLondonUKSearch for other works by this author on:
-
CHAPTER 4: Auristatin Payloads for Antibody–Drug Conjugates (ADCs)p73-99ByPeter D. SenterPeter D. SenterSearch for other works by this author on:
-
CHAPTER 5: Maytansinoid Payloads for Antibody–Drug Conjugates (ADCs)p100-116ByWayne C. WiddisonWayne C. WiddisonSearch for other works by this author on:
-
CHAPTER 6: Colchicine-, Vinblastine-, Taxol- and Eribulin-based Payloads for Antibody–Drug Conjugates (ADCs)p117-136ByArpita Velani;Arpita VelaniKing's College London, Institute of Pharmaceutical Science, School of Cancer & Pharmaceutical Sciences, Faculty of Life Sciences & MedicineFranklin–Wilkins Building, 150 Stamford StreetSE1 9NHLondonUKdavid.thurston@kcl.ac.ukSearch for other works by this author on:Syafiq Kay;Syafiq KayKing's College London, Institute of Pharmaceutical Science, School of Cancer & Pharmaceutical Sciences, Faculty of Life Sciences & MedicineFranklin–Wilkins Building, 150 Stamford StreetSE1 9NHLondonUKdavid.thurston@kcl.ac.ukSearch for other works by this author on:Earl F. Albone;Earl F. AlboneEisai Inc.210 Welsh Pool RoadExtonPennsylvania 19341USASearch for other works by this author on:David E. ThurstonDavid E. ThurstonKing's College London, Institute of Pharmaceutical Science, School of Cancer & Pharmaceutical Sciences, Faculty of Life Sciences & MedicineFranklin–Wilkins Building, 150 Stamford StreetSE1 9NHLondonUKdavid.thurston@kcl.ac.ukSearch for other works by this author on:
-
CHAPTER 7: Traditional Cytotoxic Agents as Antibody–Drug Conjugate (ADC) Payloadsp137-165ByIlona Pysz;Ilona PyszFemtogenix Ltd, Lawes Open Innovation Hub, Rothamsted ResearchWest CommonAL5 2JQHarpendenHertfordshireUKdavid.thurston@kcl.ac.ukKing's College London, Institute of Pharmaceutical Science, School of Cancer & Pharmaceutical Sciences, Faculty of Life Sciences & Medicine, Franklin–Wilkins Building150 Stamford StreetSE1 9NHLondonUKSearch for other works by this author on:Paolo Andriollo;Paolo AndriolloFemtogenix Ltd, Lawes Open Innovation Hub, Rothamsted ResearchWest CommonAL5 2JQHarpendenHertfordshireUKdavid.thurston@kcl.ac.ukKing's College London, Institute of Pharmaceutical Science, School of Cancer & Pharmaceutical Sciences, Faculty of Life Sciences & Medicine, Franklin–Wilkins Building150 Stamford StreetSE1 9NHLondonUKSearch for other works by this author on:David E. ThurstonDavid E. ThurstonFemtogenix Ltd, Lawes Open Innovation Hub, Rothamsted ResearchWest CommonAL5 2JQHarpendenHertfordshireUKdavid.thurston@kcl.ac.ukKing's College London, Institute of Pharmaceutical Science, School of Cancer & Pharmaceutical Sciences, Faculty of Life Sciences & Medicine, Franklin–Wilkins Building150 Stamford StreetSE1 9NHLondonUKSearch for other works by this author on:
-
CHAPTER 8: Topoisomerase Inhibitors as Antibody–Drug Conjugate (ADC) Payloadsp166-186ByDavid M. GoldenbergDavid M. GoldenbergSearch for other works by this author on:
-
CHAPTER 9: Duocarmycins as Antibody–Drug Conjugate (ADC) Payloadsp187-208ByAndrew M. Beekman;Andrew M. BeekmanSchool of Pharmacy, University of East Anglia, Norwich Research ParkNorwich NR4 7TJUKm.searcey@uea.ac.ukSearch for other works by this author on:Marco M. D. Cominetti;Marco M. D. CominettiSchool of Pharmacy, University of East Anglia, Norwich Research ParkNorwich NR4 7TJUKm.searcey@uea.ac.ukSearch for other works by this author on:Mark SearceyMark SearceySchool of Pharmacy, University of East Anglia, Norwich Research ParkNorwich NR4 7TJUKm.searcey@uea.ac.ukSearch for other works by this author on:
-
CHAPTER 10: CXI Dimers as Antibody–Drug Conjugate (ADC) Payloadsp209-240ByGeorge Procopiou;George ProcopiouFemtogenix Ltd., Lawes Open Innovation Hub, Rothamsted ResearchWest CommonAL5 2JQHarpendenHertfordshireUKgeorge.procopiou@femtogenix.comSearch for other works by this author on:Christopher J. O'DonnellChristopher J. O'DonnellPfizer Inc., Worldwide Research & Development445 Eastern Point RdGrotonCT 06340USASearch for other works by this author on:
-
CHAPTER 11: Duocarmycin–PBD Dimers as Antibody–Drug Conjugate (ADC) Payloadsp241-258ByThomas H. Pillow;Thomas H. PillowGenentech Inc.1 DNA WaySouth San FranciscoCA 94080USASearch for other works by this author on:Moana TercelMoana TercelAuckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, The University of AucklandPrivate Bag 92019Auckland 1142New Zealandm.tercel@auckland.ac.nzSearch for other works by this author on:
-
CHAPTER 12: Calicheamicins as Antibody–Drug Conjugate (ADC) Payloadsp259-278ByRussell G. DushinRussell G. DushinSearch for other works by this author on:
-
CHAPTER 13: Pro-pyrrolobenzodiazepines and Conjugates as Antibody–Drug Conjugate (ADC) Payloadsp279-295ByChristopher P. LeamonChristopher P. LeamonSearch for other works by this author on:
-
CHAPTER 14: Pyrrolobenzodiazepine Dimers as Antibody–Drug Conjugate (ADC) Payloadsp296-331ByPhilip W. HowardPhilip W. HowardSearch for other works by this author on:
-
CHAPTER 15: Indolinobenzodiazepine Dimers (IGNs) as Antibody–Drug Conjugate (ADC) Payloadsp332-348ByMicheal L. Miller;Micheal L. MillerImmunoGen, Inc., Department of Chemistry830 Winter StreetWalthamMassachusettsUSAmichael.miller@immunogen.comSearch for other works by this author on:Ravi V. J. ChariRavi V. J. ChariImmunoGen, Inc., Department of Chemistry830 Winter StreetWalthamMassachusettsUSAmichael.miller@immunogen.comSearch for other works by this author on:
-
CHAPTER 16: Pyridinobenzodiazepines (PDDs) as Sequence-selective DNA Mono-alkylating Antibody–Drug Conjugate (ADC) Payloadsp349-363ByNicolas Veillard;Nicolas VeillardFemtogenix LtdLawes Open Innovation Hub, Rothamsted Research, West CommonHarpendenHertfordshireAL5 2JQUKSearch for other works by this author on:Francesco Cascio;Francesco CascioFemtogenix LtdLawes Open Innovation Hub, Rothamsted Research, West CommonHarpendenHertfordshireAL5 2JQUKSearch for other works by this author on:Paul J. M. Jackson;Paul J. M. JacksonFemtogenix LtdLawes Open Innovation Hub, Rothamsted Research, West CommonHarpendenHertfordshireAL5 2JQUKSearch for other works by this author on:David E. ThurstonDavid E. ThurstonFemtogenix LtdLawes Open Innovation Hub, Rothamsted Research, West CommonHarpendenHertfordshireAL5 2JQUKKing's College London, Institute of Pharmaceutical Science, School of Cancer & Pharmaceutical Sciences, Faculty of Life Sciences & MedicineFranklin–Wilkins Building, 150 Stamford StreetSE1 9NHLondonUKdavid.thurston@kcl.ac.ukSearch for other works by this author on:
-
CHAPTER 17: Splicing Inhibitors as Antibody–Drug Conjugate (ADC) Payloadsp364-379ByChakrapani SubramanyamChakrapani SubramanyamSearch for other works by this author on:
-
CHAPTER 18: Tubulysins as Antibody–Drug Conjugate (ADC) Payloadsp380-397ByJeremy S. ParkerJeremy S. ParkerEarly Chemical Development, Pharmaceutical Sciences, IMED Biotech Unit, AstraZenecaMacclesfieldUKjeremy.parker@astrazeneca.comSearch for other works by this author on:
-
CHAPTER 19: Amatoxins as RNA Polymerase II Inhibiting Antibody–Drug Conjugate (ADC) Payloadsp398-426ByTorsten HechlerTorsten HechlerSearch for other works by this author on:
-
CHAPTER 20: Protein Toxins as Antibody–Drug Conjugate (ADC) Payloadsp427-438ByKurt R. GehlsenKurt R. GehlsenSearch for other works by this author on:
-
CHAPTER 21: Occupational Health and Safety Considerations for the Handling and Manufacture of Antibody–Drug Conjugate (ADC) Payloadsp439-460ByGeorge Procopiou;George ProcopiouFemtogenix LtdLawes Open Innovation Hub, Rothamsted Research, West CommonAL5 2JQHarpendenHertfordshireUKSearch for other works by this author on:Justin Mason-HomeJustin Mason-HomeSearch for other works by this author on:
-
CHAPTER 22: The Future of Antibody–Drug Conjugate (ADC) Payloadsp461-471ByRobert J. LutzRobert J. LutzSearch for other works by this author on:
Spotlight
Advertisement
Advertisement