title: Salmonella-mediated tumor-targeting TRAIL gene therapy significantly suppresses melanoma growth in mouse model.
abstract: Attenuated Salmonella typhimurium (S. typhimurium) strains can selectively grow and express exogenous genes in tumors for targeted therapy. We engineered S. typhimurium strain VNP20009 to secrete tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) under the control of a hypoxia-induced nirB promoter and examined the efficacy of Salmonella-mediated targeted expression of TRAIL in mice bearing melanoma tumor and in TRAIL-resistant RM-1 tumor. We found that VNP preferentially accumulated in tumor tissues and the nirB promoter effectively drove targeted expression of TRAIL. Compared with recombinant TRAIL protein and VNP20009 combination therapy, VNP20009 expressing TRAIL significantly suppressed melanoma growth but failed to suppress RM-1 tumor growth. Furthermore, we confirmed that VNP20009 expressing TRAIL yielded its antitumor effect by inducing melanoma apoptosis. Our findings indicate that Salmonella-mediated tumor-targeted therapy with TRAIL could reduce tumor growth and extend host survival.
authors: The State Key Laboratory of Pharmaceutical Biotechnology and School of Stomatology, Affiliated Stomatological Hospital, Nanjing University, Nanjing, China.
authors: Jianxiang
authors: J
authors: Chen
authors: Bingya
authors: B
authors: Yang
authors: Xiawei
authors: X
authors: Cheng
authors: Yiting
authors: Y
authors: Qiao
authors: Bo
authors: B
authors: Tang
authors: Guo
authors: G
authors: Chen
authors: Jing
authors: J
authors: Wei
authors: Xiufeng
authors: X
authors: Liu
authors: Wei
authors: W
authors: Cheng
authors: Pan
authors: P
authors: Du
authors: Xiaofeng
authors: X
authors: Huang
authors: Wenhui
authors: W
authors: Jiang
authors: Qingang
authors: Q
authors: Hu
authors: Yiqiao
authors: Y
authors: Hu
authors: Jiahuang
authors: J
authors: Li
authors: Zi-Chun
authors: ZC
authors: Hua
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001426:Bacterial Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005260:Female; D015316:Genetic Therapy; D005822:Genetic Vectors; D008546:Melanoma, Experimental / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D011401:Promoter Regions, Genetic; D012486:Salmonella typhimurium / Q000235:genetics* / Q000378:metabolism*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; C478239:NirB protein, Salmonella typhimurium; D053221:TNF-Related Apoptosis-Inducing Ligand; C505654:Tnfsf10 protein, mouse