Figure 3.

Antibody-drug conjugate mechanism of action. Once the ADC is administered, (1) it is released into the bloodstream. (2) The antibody portion of the ADC binds to overexpressed target tumor antigen/receptor (e.g., HER2). (3) Upon binding, the ADC-receptor complex undergoes receptor-mediated endocytosis, leading to the formation of endosomes (4). Within the lysosome, (5) the ADC-receptor complex is degraded, and the linker is cleaved, leading to the release of cytotoxic payloads (6). Depending on the type of payload used, (7) it will cause cell death either through DNA damage or microtubule disruption. Additionally, (8) payloads that have a membrane-permeable nature will exert the same cytotoxic effect on neighboring cells through a process known as the bystander effect, regardless of their antigen expression.