Jeremy Drees1, Michael Mertensotto2, Garvey Liu3, Jayanth Panyam3, Arnold Leonard2, Lance Augustin2, Janet Schottel4, Daniel Saltzman2. 1. Department of Surgery, University of Minnesota, Minneapolis, MN, U.S.A. dree0036@umn.edu. 2. Department of Surgery, University of Minnesota, Minneapolis, MN, U.S.A. 3. Department of Pharmaceutics, University of Minnesota, Minneapolis, MN, U.S.A. 4. Department of Biochemistry, Molecular Biology & Biophysics, University of Minnesota, Minneapolis, MN, U.S.A.
Abstract
BACKGROUND/AIM: Cancer treatment with attenuated Salmonella enterica Typhimurium (S. Typhimurium) has gained momentum in recent years. However, the effectiveness of this treatment has not been explored in autochthonous models. We report the efficacy of S. Typhimurium in mice with autochthonous mammary tumors. MATERIALS AND METHODS: S. Typhimurium attenuated by deletion of cyclic adenosine monophosphate signaling, SalpNG.1, was injected into female BALB-neuT tumor-bearing mice. Mice were monitored for efficacy and sacrificed for mechanistic studies. RESULTS: In treated mice, seven-week post-treatment tumor burden was reduced by 85% and median survival was increased by 88%. Efficacy was correlated with increased tumor-infiltrating CD8 and natural killer cells. In addition, SalpNG.1 treatment caused a systemic increase of monocytic myeloid-derived suppressor cells that accumulated to high numbers within tumor tissue. Bacteria were not detected in tumor tissue, suggesting that the observed efficacy was due to a systemic rather than a tumor-specific effect of the bacteria. CONCLUSION: S. Typhimurium treatment reduces tumor burden and increases survival in an autochthonous breast cancer model. Copyright
BACKGROUND/AIM: Cancer treatment with attenuated Salmonella entericaTyphimurium (S. Typhimurium) has gained momentum in recent years. However, the effectiveness of this treatment has not been explored in autochthonous models. We report the efficacy of S. Typhimurium in mice with autochthonous mammary tumors. MATERIALS AND METHODS:S. Typhimurium attenuated by deletion of cyclic adenosine monophosphate signaling, SalpNG.1, was injected into female BALB-neuT tumor-bearing mice. Mice were monitored for efficacy and sacrificed for mechanistic studies. RESULTS: In treated mice, seven-week post-treatment tumor burden was reduced by 85% and median survival was increased by 88%. Efficacy was correlated with increased tumor-infiltrating CD8 and natural killer cells. In addition, SalpNG.1 treatment caused a systemic increase of monocytic myeloid-derived suppressor cells that accumulated to high numbers within tumor tissue. Bacteria were not detected in tumor tissue, suggesting that the observed efficacy was due to a systemic rather than a tumor-specific effect of the bacteria. CONCLUSION:S. Typhimurium treatment reduces tumor burden and increases survival in an autochthonous breast cancer model. Copyright
Authors: Jeremy J Drees; Michael J Mertensotto; Lance B Augustin; Janet L Schottel; Daniel A Saltzman Journal: J Cancer Date: 2015-07-15 Impact factor: 4.207