Skip to main content
. Author manuscript; available in PMC: 2012 Oct 15.
Published in final edited form as: Cancer Res. 2011 Oct 15;71(20):6300–6309. doi: 10.1158/0008-5472.CAN-11-1374

Figure 1.

Figure 1

Pathways of binding, internalization and processing by immunotoxins and ADCs leading to the killing of target cells. 1. A PE-derived immunotoxin binds CD22, is internalized via clathrin-coated pits, is processed within the cell, trafficks through the ER to the cytosol where an enzymatically active fragment ADP-ribosylates EF2, which inhibits protein synthesis leading to cell death. 2. A DT-based toxin, targeted to the IL2 receptor, is internalized to endosomes where the A chain of the toxin is released to the cytosol: it also ADP-ribosylates EF2, inhibiting protein synthesis leading to cell death. 3. ADCs bind target receptors, are internalized and traffic to lysosomes. In the lysosome, drugs are cleaved from the carrier antibody and then released to the cytosol to target tubulin (for auristatin and maytansine) or DNA (for calicheamicin). The pathway for ricin-based immunotoxins (not shown) resembles that of PE except its cytosolic target is the ribosomal RNA. Ricin-mediated depurination of rRNA results in inhibition of protein synthesis.