Salmonella-mediated tumor-targeting TRAIL gene therapy significantly suppresses melanoma growth in mouse model |
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Authors: | Chen Jianxiang Yang Bingya Cheng Xiawei Qiao Yiting Tang Bo Chen Guo Wei Jing Liu Xiufeng Cheng Wei Du Pan Huang Xiaofeng Jiang Wenhui Hu Qingang Hu Yiqiao Li Jiahuang Hua Zi-Chun |
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Institution: | The State Key Laboratory of Pharmaceutical Biotechnology and School of Stomatology, Affiliated Stomatological Hospital, Nanjing University, Nanjing, China. |
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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. |
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