Systemic administration of attenuated Salmonella typhimurium in combination with interleukin-21 for cancer therapy

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Abstract
Attenuated Salmonella typhimurium (S. typhi­murium) strain VNP20009 has been employed as a powerful anticancer agent due to its selective accumulation in tumors for targeted therapy. S. typhimurium has been demonstrated to constitute a delivery tool carrying antiangiogenic or proapoptotic genes that treat cancer. The hydrodynamic tail vein (HTV) injection of naked plasmid DNA has been developed as an effective gene delivery strategy, which has been successfully used in vivo. The aim of this study was to develop a combination therapy of S. typhimurium VNP20009 and HTV injection of interleukin-21 (IL-21) expression plasmid to evaluate the antitumor potential on an experimental melanoma model. Consistent with previous results, single VNP20009 treatment was demonstrated to possess effective activities to suppress tumor growth and prolong animal survival. Moreover, HTV injection of IL-21 plasmid promoted the antitumor activities of VNP20009. The mice that were administered combined therapy exhibited smaller tumor sizes and longer survival time compared with those administered VNP20009 or IL-21 treatment alone. IL-21 induced more infiltrating natural killer (NK) and T cells to the tumor area. These findings indicated that S. typhimurium in combination with IL-21 promotes antitumor immune responses, suggesting a novel strategy in the treatment of cancer.

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