Immunological protection against HPV16 E7-expressing human esophageal cancer cell challenge by a novel HPV16-E6/E7 fusion protein based-vaccine in a Hu-PBL-SCID mouse model

Yuanzhi Lu, Zhixin Zhang, Qiao Liu, Bo Liu, Xinxin Song, Mingrong Wang, Xinhua Zhao, Qingzheng Zhao*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Increasing evidence has suggested that infection with high-risk human papillomavirus (HPVs) is closely associated with esophageal squamous cell carcinoma (ESCC) in China. The E6 and E7 oncoproteins expressed in ESCC are considered as attractive tumor-specific antigen targets for immunotherapy. We have reported that the HPV16mE6 D/mE7/TBhsp70Δ fusion protein vaccination induced powerful anti-tumor immunity against TC-1 tumor cells in a C57BL/6 mouse model. In the present study, we further evaluate the protective efficacy of this fusion protein vaccine using an HPV E7-expressing human ESCC cell line (EC9706) and a Hu-PBL-SCID mouse model. We demonstrated that immunization with the fusion protein vaccine caused significant inhibition of tumor growth with the delay time to tumor detection (tests vs. controls, 16 d vs. 9 d, p<0.01) and much smaller tumor size (p<0.01) in vivo. The inhibitory rate was ca. 69.6%, and 25% of the fusion protein vaccinated-mice remained tumor free by the end of the experiment (42 d). Furthermore, the activated lymphocytes (CD8 +) were capable of infiltrating into the tumor site, and much more apoptotic cells along with activation of caspase-3 were observed in the tumors from vaccinated-mice. Also, high expression levels of human IFN-γ, TNF-α, granzyme B and perforin were detected in the tumors from vaccinated-mice. Therefore, we concluded that the HPV16 mE6Δ/mE7/ TBhsp70Δ fusion protein vaccine is able to stimulate cellular-mediated immune response against E7-containing ESCC cells through CD8+- dependent CTL-induced apoptosis in Hu-PBL-SCID mice. These findings provide a scientific basis for HPV E7-expressing ESCC active immunotherapy.

Original languageEnglish (US)
Pages (from-to)150-156
Number of pages7
JournalBiological and Pharmaceutical Bulletin
Volume30
Issue number1
DOIs
StatePublished - 2007

Keywords

  • E6 protein
  • E7 protein
  • Esophageal squamous cell carcinoma
  • Hu-PBL-SCID mouse
  • Human papillomavirus 16(HPV16)
  • Vaccine

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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