High-efficacy targeting of colon-cancer liver metastasis with Salmonella typhimurium A1-R via intra-portal-vein injection in orthotopic nude-mouse models
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Kei Kawaguchi1,2,3, Takashi Murakami1, Atsushi Suetsugu1, Tasuku Kiyuna1, Kentaro Igarashi1, Yukihiko Hiroshima1, Ming Zhao1, Yong Zhang1, Michael Bouvet2, Bryan M. Clary2, Michiaki Unno3, Robert M. Hoffman1,2
1AntiCancer, Inc., San Diego, California, USA
2Department of Surgery, University of California San Diego, San Diego, California, USA
3Department of Surgery, Graduate School of Medicine, Tohoku University, Sendai, Japan
Robert M. Hoffman, email: [email protected]
Michiaki Unno, email: [email protected]
Bryan. M. Clary, email: [email protected]
Keywords: Salmonella typhimurium A1-R, tumor targeting, intra-portal vein injection, liver metastasis, colon cancer
Received: August 11, 2016 Accepted: September 02, 2016 Published: September 23, 2016
Liver metastasis is the main cause of colon cancer-related death and is a recalcitrant disease. We report here the efficacy and safety of intra-portal-vein (iPV) targeting of Salmonella typhimurium A1-R on colon cancer liver metastasis in a nude-mouse orthotopic model. Nude mice with HT29 human colon cancer cells, expressing red fluorescent protein (RFP) (HT29-RFP), growing in the liver were administered S. typhimurium A1-R by either iPV (1×104 colony forming units (CFU)/100 μl) or, for comparison, intra-venous injection (iv; 5×107 CFU/100 μl). Similar amounts of bacteria were delivered to the liver with the two doses, indicating that iPV delivery is 5×103 times more efficient than iv delivery. Treatment efficacy was evaluated by tumor fluorescent area (mm2) and total fluorescence intensity. Tumor fluorescent area and fluorescence intensity highly correlated (p<0.0001). iPV treatment was more effective compared to both untreated control and iv treatment (p<0.01 and p<0.05, respectively with iPV treatment with S. typhimurium arresting metastatic growth). There were no significant differences in body weight between all groups. The results of this study suggest that S. typhimurium A1-R administered iPV has potential for peri-operative adjuvant treatment of colon cancer liver metastasis.
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