Abstract
A variety of bacterial strains have been evaluated as bio-therapeutic and immunomodulatory agents to treat cancer. One such strain, Salmonella enterica serovar Typhimurium VNP20009, which is attenuated by a purine auxotrophic mutation and modified lipid A, is characterized in previous models as a safely administered, tumor colonizing agent. However, earlier work tended to use less aggressive cancer cell lines and immunocompromised animal models. Here, we investigated the safety and efficacy of VNP20009 in a highly malignant murine model of human breast cancer. Additionally, as VNP20009 has recently been found to have a defective chemotaxis system, we tested whether restoring chemotaxis would improve anti-cancer properties in this model system. Exposure to VNP20009 had no significant effect on primary mammary tumor size or pulmonary metastasis, and the tumor colonizing process appeared chemotaxis independent. Moreover, tumor-bearing mice exposed to Salmonella exhibited increased morbidity that was associated with significant liver disease. Our results suggest that VNP20009 may not be safe or efficacious when used in aggressive, metastatic breast cancer models utilizing immunocompetent animals.
Highlights
The use of bacteria as bio-therapeutic agents for cancer treatment has a long and interesting history
Our results suggest that VNP20009 may not be safe or efficacious when used in aggressive, metastatic breast cancer models utilizing immunocompetent animals
Because multiple studies suggested the importance of S. Typhimurium chemotaxis on both the ability of bacteria to colonize tumor tissue and to influence tumor growth, we investigated the effects of VNP20009 and VNP20009 cheY+ on primary mammary tumor growth in the 4T1 model
Summary
The use of bacteria as bio-therapeutic agents for cancer treatment has a long and interesting history. Some of the earliest documented, large scale observations supporting the use of bacteria as bio-therapy came from William B. Over the last few decades, numerous studies have emerged that reinvigorated the field of bacteria-based bio-therapeutics for the treatment of cancer. Several bacterial genera have been evaluated in pre-clinical cancer models, including Bifidobacterium, Clostridium and Salmonella enterica serovar Typhimurium [5,6,7]. As evidenced by the volume of studies in the current literature, Salmonella is by far the most extensively evaluated and characterized bacterial genus currently being explored as a cancer bio-therapeutic agent [8]
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