Attenuated Salmonella typhimurium invades and decreases tumor burden in neuroblastoma.

Abstract

INTRODUCTION: We have previously shown that Salmonella elicits an antitumor response against hepatic adenocarcinomatous metastases. In vitro studies have demonstrated both intracellular invasion and proliferation of Salmonella within cultured neuroblastoma cells. We sought to demonstrate in vivo invasion, proliferation, and a potential antitumor response. METHODS: A murine model for retroperitoneal neuroblastoma was established with viable neuroblastoma cells. A green fluorescent protein (GFP--Clontech, Palo Alto, CA) gene was inserted into our attenuated Salmonella species via electroporation. Fourteen days after retroperitoneal injection, the Salmonella typhimurium-pGFP construct was administered and studied. In separate experiments, the antitumor effect against neuroblastoma was studied in controls, Salmonella lacking an interleukin 2 (IL-2) gene (Sal-NG), and Salmonella containing an IL-2 gene (Salmonella-pIL2 ). RESULTS: Consistent with previous reports, 74% of mice injected were found to have recognizable tumors. Salmonella was present within tumor cells. Average tumor volumes for control, Sal-NG, and Salmonella-pIL2 mice were 2024.3, 749.5, and 332.4 mm3 , respectively (P < .0001). Tumor weights for control, Sal-NG, and Salmonella-pIL2 mice were 2.218, 0.880, and 0.377 g, respectively (P < .0001). CONCLUSIONS: Attenuated Salmonella species can now be tracked via fluorescent microscopy within tumor cells. Furthermore, an 84% reduction in tumor burden was observed in those animals gavage fed Salmonella with the IL-2 gene.