[Basics and Innovations in Antibody-Drug Conjugates]

Abstract

The efficacy of antibody-drug conjugates(ADCs)has been well-established in clinical use, prompting ongoing research and development efforts to advance the field of ADCs further. This chapter provides overview of the structure and mechanism of action of ADCs, detailing the roles of its components: the antibody, the payload, and the linker. ADCs leak from cancer vessels to bind to specific antigens on the surface of tumor cells. Upon binding and internalization, the drug is released by metabolic enzymes, such as peptidases in the lysosome. The therapeutic window of the conjugated drug is therefore expanded. To enhance the efficacy of ADCs, the chapter will also explore the development of methodologies for generating homogeneous ADCs and the concept of bystander effects, which are particularly relevant in the tumor microenvironment. Additionally, innovative approaches such as radioimmunotherapy, utilizing alpha-ray emitting radionuclides, and photoimmunotherapy, are discussed as promising next-generation ADC strategies. The integration of ADCs with immunotherapy may offer amplified effectiveness through synergistic actions. The chapter underscores that the prolonged therapeutic impact of ADCs cannot be solely attributed to the targeted delivery and controlled release of the payload. A comprehensive understanding from the perspective of cancer immunology is imperative for elucidating the underlying mechanisms contributing to their sustained efficacy.