Original Article

Cancer Gene Therapy (2012) 19, 667–674; doi:10.1038/cgt.2012.55; published online 24 August 2012

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

B G Wieking1, D W Vermeer1, W C Spanos1,2, K M Lee1, P Vermeer1, W T Lee3, Y Xu4, E S Gabitzsch4, S Balcaitis4, J P Balint Jr4, F R Jones4 and J H Lee1,2

  1. 1Cancer Biology Research Center, Sanford Research/University of South Dakota, Sioux Falls, SD, USA
  2. 2Department of Otolaryngology/Head and Neck Surgery, Sanford Health, Sioux Falls, SD, USA
  3. 3Division of Otolaryngology/Head and Neck Surgery, Duke University Medical Center, Durham, NC, USA
  4. 4Etubics Corporation, Seattle, WA, USA

Correspondence: Dr JH Lee, Cancer Biology Research Center, Sanford Research/University of South Dakota, 2301 East 60th Street North, Sioux Falls, SD 57104, USA. E-mail: John.Lee@SanfordHealth.org

Received 12 December 2011; Revised 9 July 2012; Accepted 12 July 2012
Advance online publication 24 August 2012

Top

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.

Keywords:

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