Tumor-targeted Salmonella typhimurium overexpressing cytosine deaminase: a novel, tumor-selective therapy

Methods Mol Biol. 2009;542:649-59. doi: 10.1007/978-1-59745-561-9_33.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromosomes, Bacterial / genetics
  • Cloning, Molecular
  • Cytosine Deaminase / metabolism*
  • Escherichia coli / enzymology
  • Female
  • Fluorouracil / pharmacokinetics
  • Genetic Therapy / methods*
  • Genetic Vectors / genetics
  • Mice
  • Mice, Inbred C57BL
  • Neoplasms / therapy*
  • Organ Specificity
  • Salmonella typhimurium / genetics*
  • Tissue Distribution

Substances

  • Cytosine Deaminase
  • Fluorouracil