Abstract
A tumour therapy is proposed based on attenuated Salmonella typhimurium VNP20047 expressing the Escherichia coli cytosine deaminase gene. VNP20047 was administered intravenously to B16(F10) melanoma-bearing C57BL/6 mice. VNP20047 proliferated within tumours and livers regardless of the initial inoculum dose. After 10 days the number of bacteria increased in livers up to 4.2 x 10(6) cfu/g and decreased in tumours down to 5.9 x 10(6) cfu/g. VNP20047 at 1 x 10(5) cfu/mouse, when combined with 5-fluorocytosine, inhibited tumour growth by 85% without prolonging animal survival. Histology studies revealed severe lesions in tumours and livers. These data suggest that S. typhimurium VNP20047 induced inflammatory responses, even though the strain was attenuated.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antimetabolites / therapeutic use
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Colony Count, Microbial
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Cytosine Deaminase / genetics
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Escherichia coli / enzymology
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Escherichia coli / genetics
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Flucytosine / therapeutic use
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Genes, Bacterial
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Genetic Therapy / adverse effects
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Genetic Therapy / methods*
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Inflammation / etiology
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Inflammation / pathology
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Liver / microbiology
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Liver / pathology
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Melanoma, Experimental / microbiology
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Melanoma, Experimental / pathology
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Melanoma, Experimental / therapy*
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Mice
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Mice, Inbred C57BL
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Salmonella typhimurium / genetics*
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Salmonella typhimurium / growth & development
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Salmonella typhimurium / isolation & purification
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Salmonella typhimurium / pathogenicity
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Virulence / genetics
Substances
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Antimetabolites
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Flucytosine
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Cytosine Deaminase