Over the past ten years the link between human papilloma virus (HPV) infection and squamous cell carcinoma of the oral cavity and oropharynx has been increasingly elucidated. It has become clear that a significant proportion of cancers in this region are associated with HPV, and that it is probably a causal relationship. The presence of HPV within these lesions presents unique therapeutic options, including immunotherapeutic strategies. ? ? A pre-clinical model where HPV-associated oral cancers would be useful to test such strategies. Such a model does not exist. By harnessing the unique properties of a promoter with the Epstein Barr virus genome, it is hypothesized that such a transgenic mouse strain can be created. The promoter is expressed solely within the mucosa of the oral cavity, esophagus and forestomach, and it has been used previously to create a similar transgenic mouse. With this proposal, we will place the HPV16 oncogene E7 under the control of this promoter. It is hypothesized that a unique mouse model which spontaneously develops oral cancers which express E7 will be created. ? ? This transgenic strain would provide an excellent model with which to test immunotherapeutic strategies which target E7. Clinically, patients with these cancers often exhibit peripheral tolerance to E7; they are unable to mount an E7-specific cytotoxic T-lymphocyte response. Past E7 transgenic mouse strains have varied in their ability to mount a CTL response to E7. We will characterize our mouse strain with regard to tolerance to this protein. We anticipate that peripheral tolerance will be exhibited and that this model will be a particularly clinically relevant one, reflecting many characteristics of HPV-associated head and neck cancer patients. ? ?
| Fresnay, Stephanie; Zhang, Xiaoyu; Strome, Scott E et al. (2011) Bone marrow vaccination: a novel approach to enhance antigen specific antitumor immunity. Vaccine 29:8599-605 |
