[Oral gene therapy via live attenuated Salmonella leads to tumor regression and survival prolongation in mice].
OBJECTIVE
To evaluate the feasibility of oral cytokine gene therapy against tumor using live attenuated Salmonella as a vector.


METHODS
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.


RESULTS
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).


CONCLUSIONS
Oral gene therapy using live attenuated Salmonella can be potentially a simple, effective and above all, safe means for tumor treatment.
Qi
Huan
H
Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. qihuan@fimmu.com
Li
Yu-hua
YH
Zheng
Shao-bin
SB
D000284:Administration, Oral; D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000628:therapy; D005434:Flow Cytometry; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D018664:Interleukin-12 / Q000235:genetics* / Q000378:metabolism; D015674:Mammary Neoplasms, Animal / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D009374:Neoplasms, Experimental / Q000628:therapy*; D012486:Salmonella typhimurium / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D014613:Vaccines, Attenuated / Q000276:immunology
D014613:Vaccines, Attenuated; D049452:Green Fluorescent Proteins; D018664:Interleukin-12