Fig. 2.

 The free ADC binds specifically to the antigen receptor on the surface of the target cell (tumour cell). Binding to the antigen results in receptor-mediated endocytosis (internalisation). The ADC enters the endosome. The cytotoxic drug (payload) is released intracellularly. In linkers that cannot be cleaved, the payload is released via lysosomal “trafficking” – the ADC complex is degraded by lysosomal enzymes. Since the linker cannot be cleaved, in this case the linker plus one amino acid of the antibody will still be attached to the payload. Linkers that can be cleaved, on the other hand, are cleaved off thereby releasing the pure active ingredient. By detaching the linker, the payload does not have a linker component. As soon as the payload is released, it binds to the intracellular target and induces cell death (apoptosis) 38 .