Abstract
Transforming growth factor-alpha (TGF alpha)-pseudomonas exotoxin-40 (PE40) is a chimeric protein consisting of an N-terminal TGF alpha domain fused to a C-terminal 40-kDa segment of the pseudomonas exotoxin A protein. TGF alpha-PE40 exhibits the receptor binding activity of TGF alpha and the cell killing activity of PE40. In the current study, we report that a modified TGF alpha-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.
MeSH terms
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ADP Ribose Transferases*
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Animals
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Antineoplastic Agents / metabolism
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Antineoplastic Agents / pharmacology*
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Antineoplastic Agents / therapeutic use
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Bacterial Toxins / metabolism
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Bacterial Toxins / pharmacology
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Bacterial Toxins / therapeutic use
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Cell Division / drug effects
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Cell Line
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Cell Line, Transformed
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ErbB Receptors / metabolism
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Exotoxins / metabolism
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Exotoxins / pharmacology*
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Exotoxins / therapeutic use
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Female
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Mice
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Mice, Nude
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Neoplasm Transplantation
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Neoplasms, Experimental / drug therapy
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Pseudomonas aeruginosa Exotoxin A
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Pseudomonas*
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Recombinant Fusion Proteins / metabolism
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Recombinant Fusion Proteins / pharmacology*
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Recombinant Fusion Proteins / therapeutic use
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Transforming Growth Factor alpha / metabolism
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Transforming Growth Factor alpha / pharmacology*
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Transforming Growth Factor alpha / therapeutic use
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Virulence Factors*
Substances
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Antineoplastic Agents
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Bacterial Toxins
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Exotoxins
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Recombinant Fusion Proteins
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Transforming Growth Factor alpha
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Virulence Factors
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ADP Ribose Transferases
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ErbB Receptors