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.
Inhoudsopgave
Introduction to Antibody-Drug Conjugates (ADCs); Design Factors Important for Antibody-Drug Conjugate (ADC) Payloads; Use of Molecular Modelling Techniques in Antibody-Drug Conjugate (ADC) Payload Discovery and Development; Auristatin Payloads for Antibody-Drug Conjugates (ADCs); Maytansinoid Payloads for Antibody-Drug Conjugates (ADCs); Colchicine-, Vinblastine-, Taxol- and Eribulin-based Payloads for Antibody-Drug Conjugates (ADCs); Traditional Cytotoxic Agents as Antibody-Drug Conjugate (ADC) Payloads; Topoisomerase Inhibitors as Antibody-Drug Conjugate (ADC) Payloads; Duocarmycins as Antibody-Drug Conjugate (ADC) Payloads; CXI Dimers as Antibody-Drug Conjugate (ADC) Payloads; Duocarmycin-PBD Dimers as Antibody-Drug Conjugate (ADC) Payloads; Calicheamicins as Antibody-Drug Conjugate (ADC) Payloads; Pro-pyrrolobenzodiazepines and Conjugates as Antibody-Drug Conjugate (ADC) Payloads; Pyrrolobenzodiazepine Dimers as Antibody-Drug Conjugate (ADC) Payloads; Indolinobenzodiazepine Dimers (IGNs) as Antibody-Drug Conjugate (ADC) Payloads; Pyridinobenzodiazepines (PDDs) as Sequence-selective DNA Mono-alkylating Antibody-Drug Conjugate (ADC) Payloads; Splicing Inhibitors as Antibody-Drug Conjugate (ADC) Payloads; Tubulysins as Antibody-Drug Conjugate (ADC) Payloads; Amatoxins as RNA Polymerase II Inhibiting Antibody-Drug Conjugate (ADC) Payloads; Protein Toxins as Antibody-Drug Conjugate (ADC) Payloads; Occupational Health and Safety Considerations for the Handling and Manufacture of Antibody-Drug Conjugate (ADC) Payloads; The Future of Antibody-Drug Conjugate (ADC) Payloads
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