Figures & data
Figure 1. Two major mechanisms of action have been described for ADC, cytotoxic targets microtubules disrupting the microtubule network (5a) or DNA targeted cytotoxic enter target cell’s nucleus and binds to the minor groove of the DNA blocking replication (5b); some cytotoxic payloads are released from the cell and may cross the membrane of neighboring cells causing bystander effect killing while others do not (e.g. DM1). The ADC first enters the cell upon binding to the tumor target cell’s antigen (1); whereby the ADC-antigen complex undergoes internalization into the endosome (2); lysosomes then merge with the endosome inducing acidification and enzymatic reactions (3); the acidic environment and enzymes mediate cleavage of linkers, releasing payloads into target cell cytosol (4); Whereby the cytotoxic works on the microtubule (5a) or DNA minor groove (5b). Ultimately the damaged caused to the target cells results in apoptosis (6).
Figure 2. Summary of ADC targets under clinical development. Source: Clinicaltrials.gov as of October 3, 2012.
