Vasculature disruption enhances bacterial targeting of autochthonous tumors

Jeremy J. Drees, Michael J. Mertensotto, Lance B. Augustin, Janet L. Schottel, Daniel A. Saltzman

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Attenuated Salmonella enterica serovar Typhimurium (S. Typhimurium) has been developed as a vector to deliver therapeutic agents to tumors. The potential of S. Typhimurium in cancer therapy is largely due to its reported propensity to accumulate at greater than 1,000-fold higher concentrations in tumors relative to healthy tissues. In this study, we compared bacterial colonization of tumors in a subcutaneous transplantation model with a more clinically relevant autochthonous tumor model. Following intravenous administration of attenuated S. Typhimurium strain SL3261, we observed approximately 10,000-fold less bacteria in autochthonous tumors that sporadically develop in transgenic BALB-neuT mice compared to tumors developed from subcutaneous transplantation of 4T1 murine breast cancer cells in BALB/c mice. Treatment of BALB-neuT mice with a vasculature-disrupting agent (VDA) prior to bacterial treatment caused necrosis of tumor tissue and significantly increased the bacterial targeting of autochthonous tumors by approximately 1,000-fold. These observations emphasize the importance of appropriate model selection in developing bacteria-based cancer therapies and demonstrate the potential of combining VDA pre-treatment with bacteria to facilitate targeting of clinically relevant tumors.

Original languageEnglish (US)
Pages (from-to)843-848
Number of pages6
JournalJournal of Cancer
Volume6
Issue number9
DOIs
StatePublished - Jan 1 2015

Keywords

  • 4T1
  • Autochthonous
  • BALB-neuT
  • Breast cancer
  • Cancer therapy
  • Combretastatin A-4
  • Necrosis
  • Salmonella
  • Spontaneous
  • Tumor-targeting
  • Vasculature disruption

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