Biological activity of a transforming growth factor-alpha-Pseudomonas exotoxin fusion protein in vitro and in vivo

Summary Transforming growth factor-alpha (TGF)-pseudomonas exotoxin-40 (PE40) is a chimeric protein consisting of an N-terminal TGF domain fused to a C-terminal 40-kDa segment of the pseudomonas exotoxin A protein. TGF-PE40 exhibits the receptor binding activity of TGF and the cell killing activity of PE40. In the current study, we report that a modified TGF-PE40 derivative significantly prolongs the survival of nude mice bearing tumors derived from cell lines which express the epidermal growth factor receptor (EGFR). In addition, the therapeutic benefit of this protein is mediated by specific binding to the EGF receptor. These results indicate that a therapeutic window exists in vivo for the use of some growth factor-toxin fusion proteins as anticancer agents.