Fig. 1

Structure and mechanism of action of conventional ADCs. ADCs consist of three essential components: a monoclonal antibody that binds to an antigen primarily expressed on the surface of tumor cells, providing specificity in targeting tumor cells; a linker that prevents premature release of the payload in the bloodstream but instead releases it in the tumor cells; and a cytotoxic payload that triggers tumor cell death by targeting critical components such as DNA, microtubules, and topoisomerase. ADC cytotoxicity involves a series of sequential stages: ① binding of the antibody to the antigen, ② internalization of the ADC-antigen complex, ③ degradation of the ADC in the lysosomes, ④ release of the payload in the cytoplasm, ⑤ its interaction with the target; ⑥ possible discharge of a fraction of the payload into the extracellular milieu, ⑦ subsequent occurrence of the bystander effect where it is internalized by neighboring cells in the tumor microenvironment. Abbreviation: TME, tumor microenvironment