Monotherapy with a tumor-targeting mutant of S. typhimurium inhibits liver metastasis in a mouse model of pancreatic cancer

Clinton Yam, Ming Zhao, Katsuhiro Hayashi, Huaiyu Ma, Hiroyuki Kishimoto, Michele McElroy, Michael Bouvet, Robert M. Hoffman

Research output: Contribution to journalArticlepeer-review

109 Citations (Scopus)

Abstract

Cancer of the exocrine pancreas is the fourth leading cause of cancer deaths in the United States. Currently, surgical resection is the only hope for cure. The majority of patients present with locally-advanced or metastatic disease. The most common site for distant metastasis is the liver. We report here a modified auxotrophic strain of S. typhimurium that can target and inhibit the growth of liver metastasis in a mouse model of pancreatic cancer. This strain of S. typhimurium is auxotrophic (leucine-arginine dependent) but apparently receives sufficient nutritional support from tumor tissue. To increase tumor targeting ability and tumor killing efficacy, this strain was further modified by re-isolation from a tumor growing in a nude mouse and termed A1-R. In the present study, we demonstrate the efficacy of locally- as well as systemically-administered A1-R on liver metastasis of pancreatic cancer. Mice treated with A1-R given locally via intrasplenic injection or systemically via tail vein injection had a much lower hepatic and splenic tumor burden compared with control mice. Systemic treatment with intravenous A1-R also increased survival time. All results were statistically significant. This study suggests the clinical potential of bacterial treatment of a critical metastatic target of pancreatic cancer.

Original languageEnglish
Pages (from-to)248-255
Number of pages8
JournalJournal of Surgical Research
Volume164
Issue number2
DOIs
Publication statusPublished - Dec 2010

Keywords

  • bacterial therapy
  • imaging
  • nude mouse
  • orthotopic model
  • pancreatic cancer
  • red fluorescent protein

ASJC Scopus subject areas

  • Surgery

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