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

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.
AuthorsShaochun Chen, Chaowei Liao, Yiukay Lai, Yan Fan, Gang Lu, Hua Wang, Xiaoai Zhang, Marie C M Lin, Shuilong Leng, Hsiang-Fu Kung
JournalActa biochimica et biophysica Sinica (Acta Biochim Biophys Sin (Shanghai)) Vol. 46 Issue 1 Pg. 6-14 (Jan 2014) ISSN: 1745-7270 [Electronic] China
PMID24240707 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents
  • Bacterial Toxins
  • Cancer Vaccines
  • DNA-Binding Proteins
  • E6 protein, Human papillomavirus type 18
  • Exotoxins
  • Oncogene Proteins, Fusion
  • Oncogene Proteins, Viral
  • Papillomavirus E7 Proteins
  • Papillomavirus Vaccines
  • Virulence Factors
  • oncogene protein E7, Human papillomavirus type 16
  • ADP Ribose Transferases
  • Pseudomonas aeruginosa exotoxin A
  • Cisplatin
Topics
  • ADP Ribose Transferases (therapeutic use)
  • Animals
  • Antineoplastic Agents (therapeutic use)
  • Bacterial Toxins (therapeutic use)
  • Cancer Vaccines (immunology)
  • Cell Line, Tumor
  • Cisplatin (therapeutic use)
  • DNA-Binding Proteins (therapeutic use)
  • Drug Synergism
  • Exotoxins (therapeutic use)
  • Mice
  • Oncogene Proteins, Fusion (immunology, therapeutic use)
  • Oncogene Proteins, Viral (therapeutic use)
  • Papillomavirus E7 Proteins (therapeutic use)
  • Papillomavirus Vaccines (immunology, therapeutic use)
  • Virulence Factors (therapeutic use)

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