Bacterial cancer therapy using the attenuated fowl-adapted serovar Gallinarum.

We report here a novel anti-cancer therapy based on an avian-host-specific serotype serovar Gallinarum () deficient in ppGpp synthesis. To monitor the tumor targeting, a bioluminescent ΔppGpp was constructed and injected intravenously into mice bearing syngeneic and human xenograft tumors. Strong bioluminescent signals were detected specifically in all grafted tumors at 2 days post-injection (dpi). The bacterial counts in normal and tumor tissue at 1 dpi revealed that ΔppGpp reached >10 CFU/g in tumor tissue and 10-10 CFU/g in endothelial organs; counts were much lower in other organs. At 16 dpi, ΔppGpp counts in tumor tissue decreased to ∼10 CFU/g, while those in the other organs became undetectable. A strong anti-cancer effect was observed after the injection of ΔppGpp into BALB/c mice grafted with CT26 colon cancer cells. This could be attributed to reduced virulence, which allowed the administration of at least a 10-fold greater dose (10 CFU) of ΔppGpp than other attenuated strains of serovar Typhimurium (≤10 CFU). An advantage of the avian-specific as a cancer therapeutic should be a reduced capacity to cause infections or harm in humans.