title: Systemic administration of attenuatedSalmonella typhimuriumin combination with interleukin-21 for cancer therapy.
abstract: AttenuatedSalmonella typhimurium(S. typhimurium) strain VNP20009 has been employed as a powerful anticancer agent due to its selective accumulation in tumors for targeted therapy.S. typhimuriumhas 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 usedin vivo. The aim of this study was to develop a combination therapy ofS. typhimuriumVNP20009 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 thatS. typhimuriumin combination with IL-21 promotes antitumor immune responses, suggesting a novel strategy in the treatment of cancer.
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, Jiangsu 210093;
authors.forename: Yuxuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, Jiangsu 210093;
authors.forename: Jianxiang
authors.initials: J
authors.lastname: Chen
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, Jiangsu 210093; ; Changzhou High-Tech Research Institute of Nanjing University and Jiangsu TargetPharma Laboratories Inc., Changzhou 213164, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Tang
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, Jiangsu 210093;
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: The State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, Jiangsu 210093; ; Changzhou High-Tech Research Institute of Nanjing University and Jiangsu TargetPharma Laboratories Inc., Changzhou 213164, P.R. China.
authors.forename: Zi-Chun
authors.initials: ZC
authors.lastname: Hua
keywords: Salmonella typhimurium; interleukin-21; melanoma