Abstract
Most small cell lung cancers (SCLCs) ectopically express high levels of the c-kit receptor. We have examined if the receptor can serve as a target for a chimeric toxin, mSCF-PE40 composed of murine stem cell factor (SCF) genetically fused to the N terminus of a modified form of Pseudomonas exotoxin (PE) lacking its cell recognition domain. Selective cytotoxicity was found for human c-kit receptor-negative cells. This agent thus warrants further evaluation for therapy of human CSLCs.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ADP Ribose Transferases*
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Animals
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Bacterial Toxins / genetics*
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Carcinoma, Small Cell / drug therapy
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Carcinoma, Small Cell / metabolism*
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Cell Survival / drug effects
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Dose-Response Relationship, Drug
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Exotoxins / genetics*
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Female
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Humans
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Lung Neoplasms / drug therapy
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Lung Neoplasms / metabolism*
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Mice
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Proto-Oncogene Proteins c-kit / drug effects
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Proto-Oncogene Proteins c-kit / metabolism*
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Pseudomonas aeruginosa / genetics*
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Pseudomonas aeruginosa Exotoxin A
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Recombinant Fusion Proteins / pharmacology*
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Stem Cell Factor / genetics*
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Tumor Cells, Cultured / drug effects
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Virulence Factors*
Substances
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Bacterial Toxins
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Exotoxins
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Recombinant Fusion Proteins
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Stem Cell Factor
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Virulence Factors
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ADP Ribose Transferases
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Proto-Oncogene Proteins c-kit