Genetically engineered Salmonella typhimurium as an imageable therapeutic probe for cancer

Cancer Res. 2010 Jan 1;70(1):18-23. doi: 10.1158/0008-5472.CAN-09-3453. Epub 2009 Dec 22.

Abstract

Tumor-targeting bacteria have been studied in terms of their ability to visualize the infection pathway (through imaging probes) or to carry therapeutic molecules to tumors. To integrate these monitoring and therapeutic functions, we engineered attenuated Salmonella typhimurium defective in guanosine 5'-diphosphate-3'-diphosphate synthesis to carry cytotoxic proteins (cytolysin A) and express reporter genes. We successfully visualized the therapeutic process with these engineered bacteria in mice and found that they often mediated complete tumor (CT-26) eradication on cytotoxic gene induction. Furthermore, treatment with the engineered bacteria markedly suppressed metastatic tumor growth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Line, Tumor
  • Diagnostic Imaging / methods
  • Genetic Engineering / methods*
  • Genetic Therapy / methods*
  • Genetic Vectors / therapeutic use*
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Neoplasms / therapy*
  • Perforin / genetics*
  • Perforin / therapeutic use
  • Promoter Regions, Genetic
  • Salmonella typhimurium / genetics*
  • bcl-Associated Death Protein / genetics

Substances

  • bcl-Associated Death Protein
  • Perforin