Efficacy of a genetically modified Salmonella typhymurium against metastatic osteosarcoma in an orthotopic mouse model
R. M. Hoffman, M. Zhao and K. Hayashi
AntiCancer, Inc., San Diego, CA
Background: We have previously developed a genetically-modified strain of S. typhimurium, selected for tumor targeting and therapy in vivo. Normal tissue is cleared of these bacteria even in immunodeficient athymic mice with no apparent side effects. Methods: In this study, the tumor-targeting strain of S. typhimurium, termed A1-R, was administered i.v. to nude mice which have primary bone tumor and lung metastasis. Primary bone tumor was obtained by orthotopic intratibial injection of 5 x 105143B-RFP (red fluorescent protein) human osteosarcoma cells. One group of mice was treated with A1-R and another group was used a as control. A1-R (5 x 107 colony-forming units) was injected in the tail vein three times on weekly basis. On day 28, lung samples were excised and observed with the Olympus OV100 Small Animal Imaging System. Results: The size of the primary tumor and RFP intensity of lung metastasis were measured. Primary bone tumor size (fluorescence area [mm2]) was 232 ± 70 in the untreated group and 95 ± 23 in the treated group (P<0.05). RFP intensity of the lung metastasis was 3 ± 1.5 x 106in the untreated group and 0.42 ± 0.33 x 106 in the treated group (P<0.05). No toxicity was observed in the treated mice. Conclusions: Therefore, bacterial treatment was effective for both primary bone tumor and lung metastasis. Treatment with the tumor-targeting but non-toxic mutant of S. typhimuriumis a promising approach to therapy of metastatic osteosarcoma.
No significant financial relationships to disclose.