fig2

Figure 2. General mechanism of action of an antibody drug conjugate (ADC). A: The antibody binds to the HER2 receptor (RT) in the tumor cell and initiates the internalization process. B: The ADC-RT complex forms an endosome. C: Lysosomal degradation of the endosome releases the payload to the cytoplasm. D: The payload produces various cytotoxic effects, such as the following: D1, DNA damage, as with the topoisomerase I inhibitor in trastuzumab deruxtecan; D2, microtubule assembly interference, as with DM1 in trastuzumab emtansine; and E, bystander killing effect in neighbor tumor cells not expressing the antigen. After payload liberation in the tumor microenvironment by proteases, the payload, with cell membrane permeability, exhibits cytotoxic effects in neighboring tumor cells.