Chimeric fusion proteins--Pseudomonas exotoxin-based

Abstract

Recombinant fusion toxins have several potential advantages over conventional immunotoxin chemical conjugates, including (i) a defined toxin-ligand junction; (ii) efficient and relatively inexpensive production in large scale from bacteria; (iii) shorter plasma half-lives which might avoid diffuse endothelial damage which leads to vascular leak syndrome (VLS); and (iv) ability to genetically engineer mutations in the recombinant toxin to increase its potency or lower its non-specific toxicity. Two major varieties of recombinant fusion toxins include growth factor fusion toxins, containing a growth factor fused to truncated toxin, and recombinant immunotoxins, containing the variable fragments of an antibody fused to truncated toxin. In either case the ligand is used to bind selectively to tumor cells while the toxin kills the target cell following internalization. The bacterial toxins Pseudomonas exotoxin and diphtheria toxin are most often used for making recombinant fusion toxins. This review will focus on several agents containing truncated Pseudomonas exotoxin, which are undergoing preclinical and clinical development.