Oncotarget

Research Papers:

Inhibition of spontaneous and experimental lung metastasis of soft-tissue sarcoma by tumor-targeting Salmonella typhimurium A1-R

Shinji Miwa _, Yong Zhang, Kyung-Eun Baek, Fuminari Uehara, Shuya Yano, Mako Yamamoto, Yukihiko Hiroshima, Yasunori Matsumoto, Hiroaki Kimura, Katsuhiro Hayashi, Norio Yamamoto, Michael Bouvet, Hiroyuki Tsuchiya, Robert M. Hoffman and Ming Zhao

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Oncotarget. 2014; 5:12849-12861. https://doi.org/10.18632/oncotarget.2561

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Abstract

Shinji Miwa1,2,3, Yong Zhang1,2, Kyung-Eun Baek1, Fuminari Uehara1,2, Shuya Yano1,2, Mako Yamamoto1,2, Yukihiko Hiroshima1,2, Yasunori Matsumoto1,2, Hiroaki Kimura3, Katsuhiro Hayashi3, Norio Yamamoto3, Michael Bouvet2, Hiroyuki Tsuchiya3, Robert M. Hoffman1,2, Ming Zhao1

1AntiCancer, Inc., San Diego, California, USA

2Department of Surgery, University of California, San Diego, San Diego, California, USA

3Department of Orthopedic Surgery, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Ishikawa, Japan

Correspondence to:

Robert M. Hoffman or Ming Zhao, e-mail: all@anticancer.com

Keywords: HT-1080; orthotopic model; nude mice; lung metastasis; bacterial therapy

Received: August 22, 2014     Accepted: October 01, 2014     Published: December 30, 2014

ABSTRACT

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.


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