- Miwa, Shinji;
- Zhang, Yong;
- Baek, Kyung-Eun;
- Uehara, Fuminari;
- Yano, Shuya;
- Yamamoto, Mako;
- Hiroshima, Yukihiko;
- Matsumoto, Yasunori;
- Kimura, Hiroaki;
- Hayashi, Katsuhiro;
- Yamamoto, Norio;
- Bouvet, Michael;
- Tsuchiya, Hiroyuki;
- Hoffman, Robert M;
- Zhao, Ming
Prognosis of patients with lung metastases of soft-tissue sarcoma is still poor. Therefore, novel systemic therapy is needed to improve the survival of soft-tissue sarcoma. In the present study, tumor-targeting therapy with a genetically-modified auxotrophic strain of Salmonella typhimurium, termed A1-R, was evaluated. Mouse models of primary soft tissue sarcoma and spontaneous lung metastasis were obtained by orthotopic intra-muscular injection of HT1080-RFP human fibrosarcoma cells. S. typhimurium A1-R was administered from day 14, once a week for two weeks. On day 28, lung samples were excised and observed with a fluorescence imaging system. The number of lung metastasis was 8.8 ± 3.4 in the untreated group and 0.8 ± 0.8 in the treated group (P = 0.024). A mouse model of experimental lung metastasis was obtained by tail vein injection of HT1080-RFP cells. The mice were treated with S. typhimurium A1-R (i.v.) on day 7, once a week for three weeks. S. typhimurium A1-R significantly reduced lung metastases and improved overall survival (P = 0.004). S. typhimurium A1-R bacterial therapy has future potential for treating advanced soft tissue sarcoma and improving prognosis of patients with lung metastasis.