Salmonella typhimurium (A1-R) has been previously shown to target multiple tumor types. A1-R has been shown to prevent metastasis of the XPA-1 human pancreatic cancer cell line in nude mice. The aim of this study is the anti-tumor efficacy of A1-R against a more aggressive pancreatic cell line. Human MiaPaCa2 pancreatic cancer cells, expressing RFP, were cultured in vitro and subsequently infected with A1-R. Efficacy of infection was noted by intracellular bacteria with subsequent cell lysis and apoptosis. MiaPaCa2-RFP was implanted subcutaneously in nude mice. After tumor engraftment, the mice were subjected to intravenous therapy with A1-R (5×107 CFU) once a week for 3 weeks. The tumors were harvested and weighed after the treatment period. MiaPaCA2-RFP were subsequently surgically implanted orthotopically. Treatment was initiated 2 weeks later. Mice were treated with intravenous A1-R (5×107 CFU) once a week for 6 weeks, after which survival and tumor growth were recorded. In the subcutaneous tumor model, significant decreases in the rate of tumor growth (p = 0.049) and tumor size (p =0.004) were observed upon termination. In the orthotopic model, a significant decrease in the rate of tumor growth (p = 0.01) and increased survival was observed (p = 0.014). The mean survival of the treatment group and the control group was 49 days and 35 days, respectively. None of the mice showed any adverse events or weight loss from bacterial therapy. Further investigation will be expanded to other pancreatic cancer cell lines and human patient tumorgrafts in combination with chemotherapy with the goal of cure of pancreatic cancer.

Citation Format: Ali Maawy, Yong Zhang, Michael Bouvet, Robert M. Hoffman, Ming Zhao. Salmonella typhimurium A1-R inhibits aggressive pancreatic tumor growth and prolongs survival. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3319. doi:10.1158/1538-7445.AM2013-3319