title: Employment of Salmonella in Cancer Gene Therapy.
abstract: One of the primary limitations of cancer gene therapy is lack of selectivity of the therapeutic gene to tumor cells. Current efforts are focused on discovering and developing tumor-targeting vectors that selectively target only cancer cells but spare normal cells to improve the therapeutic index. The use of preferentially tumor-targeting bacteria as vectors is one of the innovative approaches for the treatment of cancer. This is based on the observation that some obligate or facultative-anaerobic bacteria are capable of multiplying selectively in tumors and inhibiting their growth. In this study, we exploited attenuated Salmonella as a tumoricidal agent and a vector to deliver genes for tumor-targeted gene therapy. Attenuated Salmonella, carrying a eukaryotic expression plasmid encoding an anti-angiogenic gene, was used to evaluate its' ability for tumor targeting and gene delivery in murine tumor models. We also investigated the use of a polymer to modify or shield Salmonella from the pre-existing immune response in the host in order to improve gene delivery to the tumor. These results suggest that tumor-targeted gene therapy using Salmonella carrying a therapeutic gene, which exerts tumoricidal and anti-angiogenic activities, represents a promising strategy for the treatment of tumors.
authors: Department of Microbiology, School of Medicine, China Medical University, Taichung, Taiwan. chlee@mail.cmu.edu.tw.|Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan. chlee@mail.cmu.edu.tw.
authors: Che-Hsin
authors: CH
authors: Lee
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D018274:Electroporation; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D012475:Salmonella / Q000235:genetics* / Q000378:metabolism; D014169:Transformation, Bacterial; D019076:Transgenes
keywords: Antitumor; Gene therapy; Polymer; Salmonella; Tumor targeting