PMID: 9166518May 1, 1996Paper

Targeting the epidermal growth factor receptor in breast cancer cell lines with a recombinant ligand fusion toxin (DAB389EGF)

The Cancer Journal From Scientific American
C K Osborne, E Coronado-Heinsohn

Abstract

The epidermal growth factor receptor (EGF-R) is overexpressed frequently in breast cancer and other solid tumors. Targeting this receptor with an EGF ligand fusion toxin might selectively intoxicate cancer cells while minimizing toxicity to normal cells. DAB389EGF is a recombinant fusion toxin containing the enzymatically active and membrane translocation domains of diphtheria toxin and sequences for human EGF. After binding to EGF-R, the drug is internalized, the toxin is released, and inhibition of protein synthesis and cell death ensue. We examined the cytotoxic effects of DAB389EGF on a panel of breast cancer cell lines. Protein synthesis, monolayer growth, and anchorage-independent growth were studied in human breast cancer cell lines expressing low, intermediate, or high EGF-R concentrations. DAB389EGF concentrations and duration of exposure required for maximal effects were determined. Specificity of cellular cytotoxicity was assessed by reversing the effects with excess native EGF and by investigating the activity of two mutant analogs of DAB389EGF that either lack diphtheria toxin enzymatic activity or EGF-R binding activity. DAB389EGF inhibited protein synthesis in the cell line panel to a variable degree. Cell lines ...Continue Reading

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