Pseudomonas exotoxin A: From virulence factor to anti-cancer agent

The pathogenic bacterium Pseudomonas aeruginosa has the ability to cause severe acute and chronic infections in humans. Pseudomonas exotoxin A (PE) is the most toxic virulence factor of this bacterium. It has ADP-ribosylation activity and decisively affects the protein synthesis of the host cells. The cytotoxic pathways of PE have been elucidated, and it could be shown that PE uses several molecular strategies developed under evolutionary pressure for effective killing. Interestingly, a medical benefit from this molecule has also been ascertained in recent years and several PE-based immunotoxins have been constructed and tested in preclinical and clinical trials against different cancers. In these molecules, the enzymatic active domain of PE is specifically targeted to tumor-related antigens. This review describes the current knowledge about the cytotoxic pathways of PE. Additionally, it summarizes preclinical and clinical trials of PE-based immunotoxins and furthermore discusses current problems and answers with these agents. (C) 2008 Elsevier GmbH. All rights reserved.