Generation of Chimeric Toxins

Chimeric toxins are generated by removing or crippling the receptor-binding domains of bacterial or plant toxins and substituting in their place proteins or peptides that bind mammalian cells. The cell-binding protein will then dictate which cell type the chimeric toxin will bind and kill. Gene fusions are then introduced into an appropriate expression system and recombinant chimeric toxins produced. Recombinant chimeric toxins have been made with diphtheria toxin and Pseudomonas exotoxin in combination with a variety of hormones, antibodies, and other cell-binding proteins. To be cytotoxic, chimeric toxins must have binding, translocating, and enzymatic activities. Of the chimeric toxins examined, most bind 3to 10-fold less well than the corresponding native ligands (34,38,45). The chimeric toxin IL-2-PE40 is toxic for cells and cell lines that display IL-2 receptors on their surface. IX A major clinical focus for the use of chimeric toxins is the treatment of cancer and immunological disorders.