J Cancer 2015; 6(9):843-848. doi:10.7150/jca.12491 This issue Cite
Short Research Communication
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
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