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Updated: Aug 17, 2026
Measuring Growth and Gene Expression Dynamics of Tumor-Targeted S. Typhimurium Bacteria
Published on: July 6, 2013
Attenuated Salmonella typhimurium invades and decreases tumor burden in neuroblastoma
Sean J Barnett1, Leland J Soto, Brent S Sorenson
1Department of Surgery, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
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.
Insights
Genetically modified Salmonella typhimurium successfully invaded neuroblastoma tumors in vivo. Salmonella engineered with an interleukin-2 gene significantly reduced tumor volume and weight, demonstrating a potent antitumor effect.
Area of Science:
- Oncology
- Microbiology
- Gene Therapy
Background:
- Salmonella has previously demonstrated an antitumor response against hepatic adenocarcinomatous metastases.
- In vitro studies confirmed Salmonella's intracellular invasion and proliferation within neuroblastoma cells.
- The study aimed to validate these findings in vivo, assessing invasion, proliferation, and antitumor potential.
Purpose of the Study:
- To demonstrate in vivo invasion and proliferation of attenuated Salmonella within neuroblastoma tumors.
- To evaluate the antitumor efficacy of Salmonella, particularly strains engineered with interleukin-2 (IL-2).
- To track Salmonella's presence within tumor cells using a green fluorescent protein (GFP) reporter.
Main Methods:
- A murine model of retroperitoneal neuroblastoma was established.
- Attenuated Salmonella species were engineered with a green fluorescent protein (GFP) gene.
- Tumor-bearing mice received Salmonella typhimurium-pGFP, with separate experiments comparing control, IL-2-deficient Salmonella (Sal-NG), and IL-2-containing Salmonella (Salmonella-pIL2) for antitumor effects.
Main Results:
- Salmonella was successfully detected within tumor cells in vivo.
- Mice treated with Salmonella-pIL2 showed significantly reduced average tumor volumes (332.4 mm3) compared to controls (2024.3 mm3) and Sal-NG (749.5 mm3) (P < .0001).
- Tumor weights were also significantly lower in the Salmonella-pIL2 group (0.377 g) versus controls (2.218 g) and Sal-NG (0.880 g) (P < .0001).
Conclusions:
- Attenuated Salmonella species, tracked via fluorescent microscopy, can invade tumor cells in vivo.
- Salmonella engineered to contain the interleukin-2 (IL-2) gene demonstrated a significant reduction in tumor burden.
- An 84% reduction in tumor burden was observed in mice treated with Salmonella containing the IL-2 gene.
