Tumor-Targeted Salmonella typhimurium Overexpressing Cytosine Deaminase: A Novel, Tumor-Selective Therapy
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The ideal anticancer regimen is one that is specific for cancer cells with limited toxicity to normal tissues. Genetically modified, nonpathogenic Salmonella offer a potential way to induce direct tumoricidal activity or to deliver tumoricidal agents to tumors. An attenuated strain of Salmonella typhimurium, called VNP20009, and its derivative TAPET-CD (which expresses Escherichia coli cytosine deaminase) are highly selective for tumor tissue and can deliver therapeutic proteins preferentially to tumors in preclinical models. Both VNP20009 and TAPET-CD have been investigated successfully in Phase 1 clinical trials in cancer patients.
Key Wordscytosine deaminase 5-fluorocytosine 5-fluorouracil Salmonella TAPET-CD tumor VNP20009
The authors thank Brooks Low, Samuel Miller, and John Pawelek for helpful suggestions and Kimberly Troy, Jeremy Pike, and Caroline Clairmont for technical assistance. This work was supported by Vion Pharmaceuticals, New Haven, CT.
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