Oral gene therapy via live attenuated Salmonella leads to tumor regression and survival prolongation in mice / 南方医科大学学报

ABSTRACT

<p><b>OBJECTIVE</b>To evaluate the feasibility of oral cytokine gene therapy against tumor using live attenuated Salmonella as a vector.</p><p><b>METHODS</b>A live attenuated AraA- autotrophic mutant of Salmonella typhimurium (SL3261) was used as carrier for eukaryotic expression vectors EGFPN1 and pCMVmIL-12 administered orally in BALB/c and C57BL/6 mice. After 6 weeks, the mice were challenged with 4T1 or Lewis tumor cells, respectively, and flow cytometry and confocal microscopy were used to detect the expression of green fluorescence protein (GFP) in the tissues. PCR and ELISA were performed to detect the integration and expression of mIL-12 gene, and the survival time of the mice was also recorded.</p><p><b>RESULTS</b>GFP expression and mIL-12 gene integration could be detected in the liver, spleen, intestinal, kidney and tumor tissues of the mice. The serum level of mIFN-gamma, mIL-12 increased significantly in mice with oral mIL-12 administration (P<0.05), which resulted in the survival prolongation of the mice as compared with the control mice (P<0.05).</p><p><b>CONCLUSION</b>Oral gene therapy using live attenuated Salmonella can be potentially a simple, effective and above all, safe means for tumor treatment.</p>