Figure 1.

The pathway of intravenously administered antibody-drug conjugates (ADCs) against receptors such as the transferrin receptor (TfR), toward exhibiting brain cancer cell cytotoxicity through receptor-medicated transcytosis (RMT) in the secretory pathway. The mAb-TfR complex was liberated under weakly acidic conditions in the endosomes. Furthermore, linked drugs acting as a payload were also liberated via the cleavage of pH-sensitive cleavable linkers under weakly acidic conditions in the endosomes. Drugs released into the brain parenchyma can be transported into cancer cells and can show anti-cancer activity. Y represents a monoclonal antibody (mAb). The blue sphere indicates a receptor that mediates transcytosis in the capillary endothelial cells at the blood-brain barrier. The red ovals represent a drug that is tethered with a mAb through a suitable linker. The dotted line indicates a linker contained in an ADC. The solid line represents the membrane.