Cytotoxic activity of a recombinant fusion protein between insulin-like growth factor i and Pseudomonas exotoxin
Prior, T.I.; Helman, L.J.; FitzGerald, D.J.; Pastan, I.
Cancer Research 51(1): 174-180
1991
ISSN/ISBN: 0008-5472 PMID: 1846308 Document Number: 373835
A chimeric toxin in which the cell binding domain of Pseudomonas exotoxin was replaced with mature human insulin-like growth factor I (IGF-I) was produced in Escherichia coli. This protein, IGF-I-PE40, was cytotoxic to human cell lines derived from a variety of tumor types, with a breast carcinoma line (MCF-7) and two hepatoma lines (HEP3B and HEPG2) showing the highest sensitivity to the toxin. The specificity of IGF-I-PE40 cytotoxicity was confirmed through competition with excess IGF-I and through blockage of toxin binding using an antibody specific to the type I IGF receptor. A potential interaction between the toxin and soluble IGF-binding proteins was also demonstrated. IGF-I-PE40 may be useful in the selective elimination of cells bearing the type I IGF receptor.