Systemic Targeting of Primary Bone Tumor and Lung Metastasis of High-grade Osteosarcoma in Nude Mice with a Tumor-selective Strain of Salmonella Typhimurium

We report here a new targeting strategy for primary bone tumor and lung metastasis with a modified auxotrophic strain of Salmonella typhimurium. We have previously developed the 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. 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 intra-tibial injection of 5 x 10(5) 143B-RFP (red fluorescent protein) human osteosarcoma cells. One group of mice was treated with A1-R expressing GFP (green fluorescent protein) and another group was used a as control. A1-R (5 x 10(7) colony-forming units) was injected in the tail vein three times on a weekly basis. On day 28, lung samples were excised and observed with the Olympus OV100 Small Animal Imaging System. The size of the primary tumor and RFP intensity of lung metastasis were measured. Primary bone tumor size (fluorescence area [mm(2)]) 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 10(6) in the untreated group and 0.42 +/- 0.33 x 10(6) in the treated group (p < 0.05). Therefore, bacterial treatment was effective for both primary bone tumor and lung metastasis.