Skip to main content
Log in

Engineered Salmonella typhimurium expressing E7 fusion protein, derived from human papillomavirus, inhibits tumor growth in cervical tumor-bearing mice

  • Original Research Paper
  • Published:
Biotechnology Letters Aims and scope Submit manuscript

Abstract

The tumor-suppressing effects of SipB160/HPV16 E7 fusion protein, derived from human papillomavirus, and expressed in Salmonella enterica serovar typhimurium, were evaluated in a cervical cancer model. The expressed E7 protein resulted in efficacious cytotoxicity and tumor growth retardation in TC-1 cervical cancer cells. In addition, in mice bearing TC-1 tumors, live cells of Salmonella expressing HPV16 E7 were administered orally and induced immune responses through interferon-gamma and tumor necrosis factor-alpha cytokine secretion and also suppressed tumor growth (45 %) and prolonged survival (70 %) compared with the control group. These results suggested that the SipB160/HPV16 E7 fusion protein may be a candidate cancer therapeutic agent.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Explore related subjects

Discover the latest articles and news from researchers in related subjects, suggested using machine learning.

References

  • Bolhassani A, Mohit E, Rafati S (2009) Different spectra of therapeutic vaccine development against HPV infections. Hum Vaccin 5:671–689

    Article  CAS  PubMed  Google Scholar 

  • Chen L, Ashe S, Singhal MC, Galloway DA, Hellstrom I, Hellstrom KE (1993) Metastatic conversion of cells by expression of human papilloma virus type 16 E6 and E7 genes. Proc Natl Acad Sci USA 90:6523–6527

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Galan JE, Curtiss R 3rd (1989) Cloning and molecular characterization of genes whose products allow Salmonella typhimurium to penetrate tissue culture cells. Proc Natl Acad Sci USA 86:6383–6387

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Jia LJ, Xu HM, Ma DY, Hu QG, Huang XF, Jiang WH, Li SF, Jia KZ, Huang QL, Hua ZC (2005) Enhanced therapeutic effect by combination of tumor-targeting Salmonella and endostatin in murine melanoma model. Cancer Biol Ther 4:840–845

    Article  CAS  PubMed  Google Scholar 

  • Khong HT, Restifo NP (2002) Natural selection of tumor variants in the generation of “tumor escape” phenotypes. Nat Immunol 3:999–1005

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lin KY, Lu D, Hung CF, Peng S, Huang L, Jie C, Murillo F, Rowley J, Tsai YC, He L, Kim DJ, Jaffee E, Pardoll D, Wu TC (2007) Ectopic expression of vascular cell adhesion molecule-1 as a new mechanism for tumor immune evasion. Cancer Res 67:1832–1841

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Low KB, Ittensohn M, Le T, Platt J, Sodi S, Amoss M, Ash O, Carmichael E, Chakraborty A, Fischer J, Lin SL, Luo X, Miller SI, Zheng L, King I, Pawelek JM, Bermudes D (1999) Lipid A mutant Salmonella with suppressed virulence and TNFalpha induction retain tumor-targeting in vivo. Nat Biotechnol 17:37–41

    CAS  PubMed  Google Scholar 

  • Marincola FM, Wang E, Herlyn M, Seliger B, Ferrone S (2003) Tumors as elusive targets of T-cell-based active immunotherapy. Trends Immunol 24:335–342

    Article  CAS  PubMed  Google Scholar 

  • Monie A, Hung CF, Wu TC (2007) Preventive and therapeutic HPV vaccines. Curr Opin Investig Drugs 8:1038–1050

    CAS  PubMed  Google Scholar 

  • Munger K (2002) The role of human papilloma viruses in human cancers. Front Biosci 7:d641–d649

    Article  PubMed  Google Scholar 

  • Pawelek JM, Sodi S, Chakraborty AK, Platt JT, Miller S, Holden DW, Hensel M, Low KB (2002) Salmonella pathogenicity island-2 and anticancer activity in mice. Cancer Gene Ther 9:813–818

    Article  CAS  PubMed  Google Scholar 

  • Pawelek JM, Low KB, Bermudes D (2003) Bacteria as tumour-targeting vectors. Lancet Oncol 4:548–556

    Article  PubMed  Google Scholar 

  • Slade BA, Leidel L, Vellozzi C, Woo EJ, Hua W, Sutherland A, Izurieta HS, Ball R, Miller N, Braun MM, Markowitz LE, Iskander J (2009) Postlicensure safety surveillance for quadrivalent human papilloma virus recombinant vaccine. JAMA 302:750–757

    Article  CAS  PubMed  Google Scholar 

  • Strugnell R, Dougan G, Chatfield S, Charles I, Fairweather N, Tite J, Li JL, Beesley J, Roberts M (1992) Characterization of a Salmonella typhimurium aro vaccine strain expressing the P.69 antigen of Bordetella pertussis. Infect Immun 60:3994–4002

    PubMed Central  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Im Hana for providing technical assistance. This study was supported by a grant of the KOREA UNIVERSITY, This study was also supported by NRF Fund (2013R1A1A2005567) from Government of KOREA.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yong Keun Park.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yoon, W., Choi, J.H., Kim, S. et al. Engineered Salmonella typhimurium expressing E7 fusion protein, derived from human papillomavirus, inhibits tumor growth in cervical tumor-bearing mice. Biotechnol Lett 36, 349–356 (2014). https://doi.org/10.1007/s10529-013-1370-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10529-013-1370-8

Keywords

Profiles

  1. Sinyeon Kim