Bacterial cancer therapy using the attenuated fowl-adapted Salmonela enterica serovar Gallinarum

초록

We report here a novel anti-cancer therapy based on an avian-host-specific serotype Salmonella enterica serovar Gallinarum (S. Gallinarum) deficient in ppGpp synthesis. To monitor the tumor targeting, a bioluminescent Delta ppGpp S. Gallinarum 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 Delta ppGpp S. Gallinarum reached >10(8) CFU/g in tumor tissue and 10(6)-10(7) CFU/g in endothelial organs; counts were much lower in other organs. At 16 dpi, Delta ppGpp S. Gallinarum counts in tumor tissue decreased to similar to 10(6) CFU/g, while those in the other organs became undetectable. A strong anti-cancer effect was observed after the injection of Delta ppGpp S. Gallinarum 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(8) CFU) of Delta ppGpp S. Gallinarum than other attenuated strains of S. enterica serovar Typhimurium (<= 10(7) CFU). An advantage of the avian-specific S. Gallinarum as a cancer therapeutic should be a reduced capacity to cause infections or harm in humans.

키워드