Resumen de Chapter Twelve - Antibody-Drug Conjugates
Amit Kumar, Jason White, R. James Christie, Nazzareno Dimasi, Changshou Gao
Abstract Antibody–drug conjugates (ADCs) are designed with the purpose of delivering small-molecule cytotoxic drug to antigen-expressing tumor cells by harnessing the specificity, biodistribution, and pharmacokinetics of antibodies. ADCs are comprised of three components: the antibody, the linker, and the cytotoxic agent. To achieve the desired goal of targeted therapy with anticipated efficacy and safety profiles, each ADC component must be carefully selected and optimized. In this chapter, we introduce the main concepts and technologies associated with clinical development of ADCs. Considerations regarding ADC production such as drug–antibody conjugation, linker technologies, and cytotoxic agents are discussed. In addition, we describe analytical methods to characterize ADC products for assessment of drug content and purity. Finally, mechanistic aspects ADCs in vivo and the underlying key factors effecting on- and off-target toxicities are introduced.
