Pseudomonas exotoxin (PE) or genetically modified forms of PE have been attached to monoclonal antibodies (mAbs) or growth factors to create cell-specific cytotoxic agents. Native PE attached to mAb OVB3 is cytotoxic to ovarian cancer cells, and to ovarian cancer in mice, and is being currently tested in women with ovarian cancer. Mutant PE molecules in which domain I has been replaced by TGFalpha or IL2 have been created by gene fusion and the chimeric proteins, TGFalpha-PE40 and IL2-PE40, produced in E. coli. TGFalpha-PE40 is very cytotoxic to cells with EGF receptors and IL2-PE40 is cytotoxic to cells with IL2 receptors. Such molecules may be useful in the elimination of tumor cells or other cells responsible for several human diseases.
