J Cancer 2015; 6(9):843-848. doi:10.7150/jca.12491

Short Research Communication

Vasculature Disruption Enhances Bacterial Targeting of Autochthonous Tumors

Jeremy J. Drees1, ✉, Michael J. Mertensotto1, Lance B. Augustin1, Janet L. Schottel2, Daniel A. Saltzman1

1. Department of Surgery, University of Minnesota, 195 MMC, 420 Delaware St SE, Minneapolis, Minnesota 55455, USA
2. Department of Biochemistry, Molecular Biology & Biophysics, University of Minnesota, 1479 Gortner Ave., St. Paul, MN 55108, USA

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Drees JJ, Mertensotto MJ, Augustin LB, Schottel JL, Saltzman DA. Vasculature Disruption Enhances Bacterial Targeting of Autochthonous Tumors. J Cancer 2015; 6(9):843-848. doi:10.7150/jca.12491. Available from http://www.jcancer.org/v06p0843.htm

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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.

Keywords: Salmonella, cancer therapy, tumor-targeting, breast cancer, BALB-neuT, autochthonous, spontaneous, 4T1, vasculature disruption, necrosis, combretastatin A-4