Targeted therapy of spinal cord glioma with a genetically modified Salmonella typhimurium

Abstract

Objective Spinal cord tumors are highly malignant and often lead to paralysis and death mainly due to their infiltrative nature, high recurrence rate, and limited treatment options. In this study, we measured the antitumor efficacy of the Salmonella typhimurium A1-R tumor-targeting strain, administered systemically or intrathecally, to spinal cord cancer in orthotopic mouse models. Materials and Methods Tumor fragments of U87-RFP were implanted by surgical orthotopic implantation into the dorsal site of the spinal cord. Five and ten days after transplantation, 8 mice in each group were treated with A1-R (2 × 107 cfu / 200μl i.v. injection or 2 × 106 cfu / 10μl intrathecal injection). Results The untreated mice showed progressive paralysis beginning at 6 days after tumor transplantation and developed complete paralysis between 18 to 25 days. The mice treated i.v. with A1-R had an onset of paralysis at approximately 11 days and at day-30, 5 mice developed complete paralysis, while other 3 mice had partial paralysis. Mice treated via intrathecal injection of A1-R had an onset of paralysis at approximately 18 days and one mouse was still not paralyzed at day-30. Only one mouse developed complete paralysis at day 30 in this group. The intrathecally-treated animals had a significant increase in survival over the i.v.-treated group as well as the control group. Conclusions These results suggest that S. typhimurium A1-R monotherapy can effectively treat spinal cord glioma.

Synergistic Suppression of Prostatic Cancer Cells by Coexpression of Both Murine Double Minute 2 Small Interfering RNA and Wild-Type p53 Gene In Vitro and In Vivo

“…Reportedly, Salmonella would infect and preferentially accumulate within the tumor xenograft in vivo, with a tumor/ normal tissue ratio of approximately 1000:1 (Pawelek et al, 1997). Attenuated Salmonella enterica serovar Typhi vaccine strain Ty21a (Salmonella Typhi Ty21a) is a facultative anaerobic bacterium and capable of replicating preferentially in tumor cells and has been explored for developing proteins therapeutic to tumors (Cryz et al, 1993;Kimura et al, 2010).…”

Microbial-based therapy of cancer: Current progress and future prospects

“…The same was verified in pancreatic tumors, where treatment with A1-R showed a clear reduction in the tumor size and in other primary tumoral models and metastases. 40 As an example, A1-R strain has demonstrated increased tumor regression, decreased metastasis number and enhanced animal survival in primary osteosarcoma and respective lung metastasis, 41 spinal cord glioma, 42 experimental lymph node metastasis, and in lung metastasis. 43 cancer progression in mice but have also shown the ability to induce a powerful immune response, enhancing the killing activity of NK cells and recruiting the activity of IL-2, INFγ and INFα.…”

The genetic basis of intradural spinal tumors and its impact on clinical treatment

“…For example, oligomers to hyaluronan suppressed the in vivo growth of spinal cord astrocytoma. 66 Another potential approach involves treatment with genetically modified Salmonella typhimurium to suppress in vivo growth of a spinal astrocytoma model; 58 however, the mechanism for this approach remains unknown.…”