Development of an adenoviral vaccine against E6 and E7 oncoproteins to prevent growth of human papillomavirus-positive cancer.

OBJECTIVES

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.

DESIGN

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.