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De-oncogenic HPV E6/E7 vaccine gets enhanced antigenicity and promotes tumoricidal synergy with cisplatin.

Authors
  • Chen, Shaochun
  • Liao, Chaowei
  • Lai, Yiukay
  • Fan, Yan
  • Lu, Gang
  • Wang, Hua
  • Zhang, Xiaoai
  • Lin, Marie C M
  • Leng, Shuilong
  • Kung, Hsiang-Fu
Type
Published Article
Journal
Acta Biochimica et Biophysica Sinica
Publisher
Oxford University Press
Publication Date
Jan 01, 2014
Volume
46
Issue
1
Pages
6–14
Identifiers
DOI: 10.1093/abbs/gmt121
PMID: 24240707
Source
Medline
Keywords
License
Unknown

Abstract

In order to develop more effective therapeutic vaccines against cancers with high-risk human papillomavirus (HPV) infection, it is crucial to enhance the immunogenicity, eliminate the oncogenicity of oncoproteins, and take a combination of E7- and E6-containing vaccines. It has been shown recently that PE(ΔIII)-E7-KDEL3 (E7), a fusion protein containing the HPV16 oncoprotein E7 and the translocation domain of Pseudomonas aeruginosa exotoxin A, is effective against TC-1 tumor cells inoculated in mice, therefore, we engineered PE(ΔIII)-E6-CRL-KDEL3 (E6), the de-oncogenic versions of the E7 and E6 fusion proteins [i.e. PE(ΔIII)-E7(d)-KDEL3, E7(d), and PE(ΔIII)-E6(d)-CRL-KDEL3, E6(d)] and tested the immunoefficacies of these fusion proteins as mono- and bivalent vaccines. Results indicated that the E7(d) get higher immunogenicity than its wild type and the E6 fusion proteins augmented the immunogenicity and antitumor effects of their E7 counterparts. Furthermore, the bivalent vaccine system E7(d) plus E6(d), in the presence of cisplatin, showed the best tumoristatic and tumoricidal effects against established tumors in vivo. Therefore, it can be concluded that this novel therapeutic vaccine system, upon further optimization, may shed new light on clinical management of HPV-related carcinomas.

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