1. ¹Institute of Basic Medical Sciences, National Cheng Kung University Medical College, Tainan, Taiwan
2. ²Department of Biochemistry, National Cheng Kung University Medical College, Tainan, Taiwan
3. ³Department of Microbiology and Immunology, National Cheng Kung University Medical College, Tainan, Taiwan

Correspondence: Dr Ai-Li Shiau, PhD, Department of Microbiology and Immunology, National Cheng Kung University Medical College, 1 Dashiue Road, Tainan 701, Taiwan. E-mail: alshiau@mail.ncku.edu.tw

Received 19 February 2004; Published online 17 September 2004.

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.