Dual specific antitumor effects of Semliki Forest virus-based DNA vector carrying suicide Escherichia coli purine nucleoside phosphorylase gene via Salmonella

Chen,Zhi-Hao; Huang,Ge-Ling; Tu,Ya-Qin; Jiang,Yu; Dai,Wu-Xing

doi:10.3892/ijo.2013.1900

Dual specific antitumor effects of Semliki Forest virus-based DNA vector carrying suicide Escherichia coli purine nucleoside phosphorylase gene via Salmonella

Authors:
- Zhi-Hao Chen
- Ge-Ling Huang
- Ya-Qin Tu
- Yu Jiang
- Wu-Xing Dai
View Affiliations

Affiliations: Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, P.R. China, Maternal and Child Health Hospital of Xiamen, Xiamen, P.R. China
Published online on: April 16, 2013 https://doi.org/10.3892/ijo.2013.1900
Pages: 2009-2018

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The Escherichia coli purine nucleoside phosphorylase/2-fluoro-2-deoxyadenosine (ePNP/F-dAdo) suicide system has demonstrated a powerful killing and bystander effects on tumor cells. However, several drawbacks to this approach remain to be resolved, such as the side-effects and the low efficiency of ePNP-targeted expression. A human telo-merase reverse transcriptase promoter-driven Semliki Forest virus-based DNA vector (pShT-ePNP) with high expression of the ePNP gene was constructed. Live attenuated Salmonella typhimurium 7207 (SL7207) was used initially as a vehicle to targetly transfer the large alphavirus vector into tumor cells. The in vitro quantitative analysis showed ~2-fold higher green fluorescent protein (GFP) expression for pShT-GFP than for conventional cytomegalovirus (CMV) promoter-mediated eukaryotic expression plasmids such as pIRES-GFP and the targeted expression of the ePNP gene in tumor cells was also detected by RT-PCR. After F-dAdo addition, the enzymatic conversion of F-Ado into 2-fluoroadmine (F-Ade) was tested by HPLC. Cell cytotoxicity assays showed that the significant inhibitory effect of the SL/pShT-ePNP system on tumor cells was dose- and time-dependent. Following oral administration, recombinant bacteria targetly allocated within the solid tumor and the expression of ePNP and GFP genes in vivo were detected by RT-PCR or observed by fluorescence microscopy. SL/pShT-ePNP and F-dAdo were also found to exert powerful therapeutic effects in combination against tumor growth and for prolonging the lifespan of tumor-bearing mice. These findings suggest that the SL/pShT-ePNP system may serve as a powerful strategy for tumor therapy.

View Figures

View References

1	Afshar S, Olafsen T, Wu AM and Morrison SL: Characterization of an engineered human purine nucleoside phosphorylase fused to an anti-her2/neu single chain Fv for use in ADEPT. J Exp Clin Cancer Res. 28:1472009. View Article : Google Scholar : PubMed/NCBI
2	Fukazawa T, Matsuoka J, Yamatsuji T, Maeda Y, Durbin ML and Naomoto Y: Adenovirus-mediated cancer gene therapy and virotherapy (Review). Int J Mol Med. 25:3–10. 2010.PubMed/NCBI
3	Gu J, Kagawa S, Takakura M, Kyo S, Inoue M, Roth JA and Fang B: Tumor-specific transgene expression from the human telomerase reverse transcriptase promoter enables targeting of the therapeutic effects of the Bax gene to cancers. Cancer Res. 60:5359–5364. 2000.
4	Fakhoury J, Nimmo GA and Autexier C: Harnessing telomerase in cancer therapeutics. Anticancer Agents Med Chem. 7:475–483. 2007. View Article : Google Scholar
5	Song JS: Activity of the human telomerase catalytic subunit (hTERT) gene promoter could be increased by the SV40 enhancer. Biosci Biotechnol Biochem. 68:1634–1639. 2004. View Article : Google Scholar : PubMed/NCBI
6	Liljeström P and Garoff H: A new generation of animal cell expression vectors based on the Semliki Forest virus replicon. Biotechnology. 9:1356–1361. 1991.PubMed/NCBI
7	Diciommo DP and Bremner R: Rapid, high level protein production using DNA-based Semliki Forest virus vectors. J Biol Chem. 273:18060–18066. 1998. View Article : Google Scholar : PubMed/NCBI
8	Kohno A, Emi N, Kasai M, Tanimoto M and Saito H: Semliki Forest virus-based DNA expression vector: transient protein production followed by cell death. Gene Ther. 5:415–418. 1998. View Article : Google Scholar : PubMed/NCBI
9	Quetglas JI, Ruiz-Guillen M, Aranda A, Cassales E, Bezunartea J and Smerdou C: Alphavirus vectors for cancer therapy. Virus Res. 153:179–196. 2010. View Article : Google Scholar
10	Wang WL, Xu HL, Lu RJ and Ruan L: A comparative study on SFV-based DNA vaccine and the conventional DNA vaccine. Chin J Virol. 18:325–331. 2002.
11	Juárez-Rodríguez MD, Arteaga-Cortés LT, Kader R, Curtiss R III and Clark-Curtiss JE: Live attenuated Salmonella vaccines against Mycobacterium tuberculosis with antigen delivery via the type III secretion system. Infect Immun. 80:798–814. 2012.
12	Hegazy WA and Hensel M: Salmonella enterica as a vaccine carrier. Future Microbiol. 7:111–127. 2012. View Article : Google Scholar
13	Loessner H and Weiss S: Bacteria-mediated DNA transfer in gene therapy and vaccination. Expert Opin Biol Ther. 4:157–168. 2004. View Article : Google Scholar : PubMed/NCBI
14	Jarosz M, Jazowiecka-Rakus J, Cichoń T, et al: Therapeutic antitumor potential of endoglin-based DNA vaccine combined with immunomodulatory agents. Gene Ther. 12:1038–1046. 2012.PubMed/NCBI
15	Moreno M, Kramer MG, Yim L and Chabalgoity JA: Salmonella as live Trojan horse for vaccine development and cancer gene therapy. Curr Gene Ther. 10:56–76. 2010. View Article : Google Scholar : PubMed/NCBI
16	Sorscher EJ, Peng S, Bebok Z, Allan PW, Bennett LL Jr and Parker WB: Tumor cell bystander killing in colonic carcinoma utilizing the E. coli Deo D gene and generation of toxic purines. Gene Ther. 1:233–238. 1994.PubMed/NCBI
17	Mosmann T: Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 65:551983. View Article : Google Scholar : PubMed/NCBI
18	Parker WB, Allan PW, Hassan AE, Secrist JA III, Sorscher EJ and Waud WR: Antitumor activity of 2-fluoro-2’-deoxyadenosine against tumors that express Escherichia coli purine nucleoside phosphorylase. Cancer Gene Ther. 10:23–29. 2003.
19	Wang W, Jin B, Li W, et al: Targeted antitumor effect induced by hTERT promoter mediated ODC antisense adenovirus. Mol Biol Rep. 37:3239–3247. 2010. View Article : Google Scholar : PubMed/NCBI
20	Hashimoto Y, Tazawa H, Teraishi F, et al: The hTERT promoter enhances the antitumor activity of an oncolytic adenovirus under a hypoxic microenvironment. PLoS One. 7:e392922012. View Article : Google Scholar : PubMed/NCBI
21	Zhang J, Wild J, Bieler K and Graf M: Comparative study of expression and humoral immunogenicity of HIV-1 group specific antigen Pr55∼(gag) by conventional plasmid vectors versus semliki forest virus-derived vectors. Chin J Virol. 18:529–536. 2002.
22	Brown A, Hormaeche CE, Demarco de Hormaeche R, Winther M, Dougan G, Maskell DJ and Stocker BA: An attenuated aroA Salmonella typhimurium vaccine elicits humoral and cellular immunity to cloned beta-galactosidase in mice. J Infect Dis. 155:86–92. 1987.
23	Hoiseth SK and Stocker BA: Aromatic-dependent Salmonella typhimurium are non-virulent and effective as live vaccines. Nature. 291:238–239. 1981.PubMed/NCBI
24	Darji A, Guzman CA, Gerstel B, et al: Oral somatic transgene vaccination using attenuated S. typhimurium. Cell. 91:765–775. 1997. View Article : Google Scholar : PubMed/NCBI
25	Zeng S, Zhang J, Zhang J, et al: Suppression of murine melanoma growth by a vaccine of attenuated Salmonella carrying heat shock protein 70 and Herpes simplex virus-thymidine kinase genes. Oncol Rep. 27:798–806. 2012.PubMed/NCBI
26	Fu W, Lan H, Li S, Han X, Gao T and Ren D: Synergistic antitumor efficacy of suicide/ePNP gene and 6-methylpurine 2′-deoxyriboside via Salmonella against murine tumors. Cancer Gene Ther. 15:474–484. 2008.PubMed/NCBI
27	Leitner WW, Hwang LN, deVeer MJ, et al: Alphavirus-based DNA vaccine breaks immunological tolerance by activating innate antiviral pathways. Nat Med. 9:33–39. 2003. View Article : Google Scholar : PubMed/NCBI
28	Gil J, Alcami J and Esteban M: Induction of apoptosis by double-stranded-RNA-dependent protein kinase (PKR) involves the alpha subunit of eukaryotic translation initiation factor 2 and NF-kappaB. Mol Cell Biol. 19:4653–4663. 1999.
29	Xie X, Guo J, Kong Y, et al: Targeted expression of Escherichia coli purine nucleoside phosphorylase and Fludara^® for prostate cancer therapy. J Gene Med. 13:680–691. 2011.PubMed/NCBI
30	Ueki H, Watanabe M, Kaku H, et al: A novel gene expression system for detecting viable bladder cancer cells. Int J Oncol. 41:135–140. 2012.PubMed/NCBI
31	Ambade AV, Joshi GV and Mulherkar R: Effect of suicide gene therapy in combination with immunotherapy on antitumour immune response and tumour regression in a xenograft mouse model for head and neck squamous cell carcinoma. Indian J Med Res. 132:415–422. 2010.PubMed/NCBI
32	Kuriyama S, Tsujinoue H and Yoshiji H: Immune response to suicide gene therapy. Methods Mol Med. 90:353–369. 2004.PubMed/NCBI
33	Dong B, Sun L, Wu X, et al: Vaccination with TCL plus MHSP65 induces anti-lung cancer immunity in mice. Cancer Immunol Immunother. 59:899–908. 2010. View Article : Google Scholar : PubMed/NCBI
34	Yamazaki M, Straus FH, Messina M, et al: Adenovirus-mediated tumor-specific combined gene therapy using Herpes simplex virus thymidine/ganciclovir system and murine interleukin-12 induces effective antitumor activity against medullary thyroid carcinoma. Cancer Gene Ther. 11:8–15. 2004. View Article : Google Scholar