Fig. 2

PEA-derived rITs for HER2 targeted therapy. The Ia domain (aa 1–252) in the N-terminus of PEA polypeptide is responsible for binding to the target cell, and domain II (aa 253–364) transports toxins from the cytoplasmic membrane into the cell. The domain III (aa 405–613) and last 4 residues of domain Ib are responsible for inhibition of protein synthesis. Domain Ia is removed to produce a PE40 (40 kDa). PE38 (38 kDa) is produced through removing domain Ia and amino acids 365–380 of domain Ib. PE25 (25 kDa) is produced through removing domain II from PE38, except FCS. For cancer therapy, PEAs are fused with a HER2-targeting scFv to produce rIT s. scFv mediates binding of rIT to HER2. After endocytosis, the toxin moiety released by furin cleavage at FSC, and through ADP-ribosyltransferase activity suppress the protein synthesis to induce cancer cells death. PEA Pseudomonas exotoxin A, rIT recombinant immunotoxin, FCS furin cleavage site