Development of an adenoviral vaccine against E6 and E7 oncoproteins to prevent growth of human papillomavirus-positive cancer.
OBJECTIVE
To test whether an immunization strategy that targets the E6 and E7 oncoproteins (E6/E7) may be an effective means to prevent the development of human papillomavirus (HPV)-positive head and neck squamous cell cancers using an in vivo mouse model and to determine whether such a response would prevent the establishment of viral transformed cells in vivo.


METHODS
Adenoviral recombinant vaccine expressing HPV-16 E6/E7 (adenovirus 5 E6/E7, or Ad5 E6/E7) was generated. Specificity and timing of the E6/E7-specific cellular immune response was determined in vivo. Adenovirus 5 E6/E7 efficacy and route of administration required for clearance of HPV-positive tumor cells were monitored.


RESULTS
We generated Ad5 E6/E7 oncoproteins. Splenocytes from mice immunized with Ad5 E6/E7 produced interferon (IFN)-gamma to cells expressing E6/E7 but not to cells lacking these oncoproteins. A time course of IFN-gamma response showed that E6/E7-specific IFN-gamma production is significantly increased in the first 2 weeks after administration of the vaccine and is substantially maintained for up to 70 days. Inoculated mice cleared E6/E7-expressing tumor 70 days after implantation. At all dosages of vaccine, mice inoculated with Ad5 E6/E7 completely cleared E6/E7-expressing tumor cells implanted 2 weeks after either intratracheal or submucosal inoculation, with significant E6/E7-specific IFN-gamma production.


CONCLUSIONS
Immunization with HPV-16 E6/E7 oncoproteins can be an effective method of protecting a host from E6/E7-expressing head and neck squamous cell cancers via generation of a potent immune response. Such a response may be beneficial when combined with traditional treatment such as surgery, chemotherapy, or radiotherapy, thus improving the prognosis and quality of life of patients with HPV-16-associated head and neck squamous cell cancers.
Lee
Dong Wook
DW
Department of Otolaryngology-Head and Neck Surgery, Sanford Research/USD, Sanford School of Medicine, University of South Dakota, 1310 W 22nd St, Sioux Falls, SD 57105, USA.
Anderson
Mary E
ME
Wu
Shu
S
Lee
John H
JH
D000256:Adenoviridae; D000818:Animals; D019496:Cancer Vaccines / Q000096:biosynthesis* / Q000627:therapeutic use; D002460:Cell Line; D004195:Disease Models, Animal; D005822:Genetic Vectors; D006258:Head and Neck Neoplasms / Q000276:immunology* / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D009856:Oncogene Proteins, Viral / Q000276:immunology*; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000276:immunology*; D012097:Repressor Proteins / Q000276:immunology*
D019496:Cancer Vaccines; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16