Fig. 2

Mode of action of brentuximab-vedotin. In Hodgkin lymphoma CD30 positive cells, brentuximab-vedotin is internalized via clathrin coated pits and reaches endosomes. CD30 can recycle or be newly synthesized and re-expressed at the cell surface. The anti-CD30 ADC complex reaches lysosomes where the linker is cleaved by proteases. MMAE molecules traverse the lysosomal membrane and access the cytosol. MMAE can bind the microtubules, triggering depolymerisation leading to cell death. MMAE can traverse the plasma membrane of certain cell lines and exert a toxic effect on neighbor cells (bystander effect)