Intracellular trafficking of trastuzumab emtansine (T-DM1). Binding of T-DM1 onto human epidermal growth factor receptor-2 (HER2) on the plasma membrane is followed by entry of the HER2-T-DM1 complex into the cell via receptor-mediated endocytosis. Internalized endocytic vesicles form early endosomes. The load of early endosomes can be recycled back to the cell membrane or the early endosome can mature to a lysosome. Release of DM1 occurs as a result of proteolytic degradation of the antibody part of T-DM1 in the lysosomes. Intracellular lysine (lys)-MCC-DM1 inhibits microtubule assembly, causing mitotic arrest, apoptosis, mitotic catastrophe, and disrupted intracellular trafficking. MCC, non-reducible thioether linker.