A non-oncogenic HPV 16 E6/E7 vaccine enhances treatment of HPV expressing tumors

B. G. Wieking, D. W. Vermeer, W. C. Spanos, K. M. Lee, P. Vermeer, W. T. Lee, Y. Xu, E. S. Gabitzsch, S. Balcaitis, J. P. Balint, F. R. Jones, J. H. Lee

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Human papillomaviruses (HPVs) are the causative factor for 90% of cervical cancers and 25% of head and neck cancers. The incidence of HPV positive (+) head and neck squamous cell carcinomas has greatly increased in the last 30 years. E6 and E7 are the two key viral oncoproteins that induce and propagate cellular transformation. An immune response generated during cisplatin/radiation therapy improves tumor clearance of HPV(+ ) cancers. Augmenting this induced response during therapy with an adenoviral HPV16 E6/E7 vaccine improves long-term survival in pre-clinical models. Here, we describe the generation of an HPV16 E6/E7 construct, which contains mutations that render E6/E7 non-oncogenic, while preserving antigenicity. These mutations do not allow E6/E7 to degrade p53, pRb, PTPN13, or activate telomerase. Non-oncogenic E6/E7 (E6 Δ/E7 Δ) expressed as a stable integrant, or in the E1-, E2b-adenovirus, lacks the ability to transform human cells while retaining the ability to induce an HPV-specific immune response. Moreover, E6 Δ/E7 Δ plus chemotherapy/radiation statistically enhances clearance of established HPV() cancer in vivo.

Original languageEnglish (US)
Pages (from-to)667-674
Number of pages8
JournalCancer Gene Therapy
Volume19
Issue number10
DOIs
StatePublished - Oct 1 2012

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Keywords

  • E6
  • E7
  • HPV
  • adenovirus
  • head and neck cancer
  • immunotherapy

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Cancer Research

Cite this

Wieking, B. G., Vermeer, D. W., Spanos, W. C., Lee, K. M., Vermeer, P., Lee, W. T., Xu, Y., Gabitzsch, E. S., Balcaitis, S., Balint, J. P., Jones, F. R., & Lee, J. H. (2012). A non-oncogenic HPV 16 E6/E7 vaccine enhances treatment of HPV expressing tumors. Cancer Gene Therapy, 19(10), 667-674. https://doi.org/10.1038/cgt.2012.55