Oral cytokine gene therapy against murine tumor using attenuated Salmonella typhimurium.

An attenuated strain of Salmonella typhimurium was used as a vehicle for oral gene therapy against murine tumor. Eukaryotic expression vectors containing genes of human interleukin-12 (hIL-12), human granulocyte/macrophage colony-stimulating factor (hGM-CSF), mouse (m)IL-12, mGM-CSF and green fluorescent protein (GFP) were used to transform attenuated Salmonella (SL3261), and such transformants were administered orally to BALB/c and C57BL/6 mice. As a reporter gene, GFP expression in murine liver, spleen, tumor, intestine and kidney was confirmed by confocal and flow cytometry. Soluble cytokines were detected in murine sera, and the concentrations were much higher than those of the control, which contributed to the increased number of cytotoxic T cells and prolongation of survival. Oral cytokine gene therapy using live attenuated Salmonella demonstrated a significant protection against the development of two unrelated murine tumors. These results suggest that such gene therapy has the potential to be simple, effective and (above all) safe against tumor.