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

Cancer Gene Therapy volume 19, pages 667–674 (2012)Cite this article

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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 (E6Δ/E7Δ) 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, E6Δ/E7Δ plus chemotherapy/radiation statistically enhances clearance of established HPV(+) cancer in vivo.

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Acknowledgements

Susan Puumala PhD-Biostatistics, Satoshi Nagat PhD-Immunology consultant, Cathy Christopherson-manuscript preparation. JHL supported by NIDCR 7R01DE018386-03 grant and subaward 3SB161 State of South Dakota-2010 Initiative.

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Authors and Affiliations

  1. Cancer Biology Research Center, Sanford Research/University of South Dakota, Sioux Falls, SD, USA

    B G Wieking, D W Vermeer, W C Spanos, K M Lee, P Vermeer & J H Lee

  2. Department of Otolaryngology/Head and Neck Surgery, Sanford Health, Sioux Falls, SD, USA

    W C Spanos & J H Lee

  3. Division of Otolaryngology/Head and Neck Surgery, Duke University Medical Center, Durham, NC, USA

    W T Lee

  4. Etubics Corporation, Seattle, WA, USA

    Y Xu, E S Gabitzsch, S Balcaitis, J P Balint Jr & F R Jones

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  1. B G Wieking
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Correspondence to J H Lee.

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Wieking, B., Vermeer, D., Spanos, W. et al. A non-oncogenic HPV 16 E6/E7 vaccine enhances treatment of HPV expressing tumors. Cancer Gene Ther 19, 667–674 (2012). https://doi.org/10.1038/cgt.2012.55

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  • DOI: https://doi.org/10.1038/cgt.2012.55

Keywords

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

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