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Systemic administration of attenuated Salmonella choleraesuis carrying thrombospondin-1 gene leads to tumor-specific transgene expression, delayed tumor growth and prolonged survival in the murine melanoma model

Cancer Gene Therapy volume 12, pages 175–184 (2005)Cite this article

Abstract

Some anaerobic and facultative anaerobic bacteria have been used experimentally as anticancer agents because of their selective growth in the hypoxia regions of solid tumors after systemic administration. We have previously shown the feasibility of using attenuated Salmonella choleraesuis as a gene delivery vector. In this study, we exploited S. choleraesuis carrying thrombospondin-1 (TSP-1) gene for treating primary melanoma and experimental pulmonary metastasis in the syngeneic murine B16F10 melanoma model. Systemic administration of S. choleraesuis allowed targeted gene delivery to tumors. The bacteria accumulated preferentially in tumors over livers and spleens at ratios ranging from 1000:1 to 10,000:1. The level of transgene expression via S. choleraesuis-mediated gene transfer in tumors could reach more than 1800-fold higher than in livers and spleens. Notably, bacterial accumulation was also observed in the lungs with metastatic nodules, but not in healthy lungs. When administered into mice bearing subcutaneous or pulmonary metastatic melanomas, S. choleraesuis carrying TSP-1 gene significantly inhibited tumor growth and enhanced survival of the mice. Immunohistochemical studies in the tumors from these mice displayed decreased intratumoral microvessel density. Taken together, these findings suggest that TSP-1 gene therapy delivered by S. choleraesuis may be effective for the treatment of primary as well as metastatic melanomas.

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Acknowledgements

This work was supported by Grants (NSC 91-3112-B-006-013 and NSC 92-3112-B-006-007) from the National Science Council, Taiwan.

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Authors and Affiliations

  1. Institute of Basic Medical Sciences, National Cheng Kung University Medical College, Tainan, Taiwan

    Che-Hsin Lee, Chao-Liang Wu & Ai-Li Shiau

  2. Department of Biochemistry, National Cheng Kung University Medical College, Tainan, Taiwan

    Chao-Liang Wu

  3. Department of Microbiology and Immunology, National Cheng Kung University Medical College, Tainan, Taiwan

    Ai-Li Shiau

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  1. Che-Hsin Lee
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Correspondence to Ai-Li Shiau.

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Lee, CH., Wu, CL. & Shiau, AL. Systemic administration of attenuated Salmonella choleraesuis carrying thrombospondin-1 gene leads to tumor-specific transgene expression, delayed tumor growth and prolonged survival in the murine melanoma model. Cancer Gene Ther 12, 175–184 (2005). https://doi.org/10.1038/sj.cgt.7700777

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