Development of a therapeutic vaccination strategy against cervical neoplasia

The aim of the studies described in this thesis was to investigate the effi cacy of a therapeutic immunization strategy against cervical cancer and premalignant cervical disease. Cervical cancer is caused by persistent infection with high-risk human papillomavirus (HPV). Two of the early proteins of these high-risk HPV, E6 and E7, interact with the cell cycle regulation proteins p53 and pRb, respectively, and can cause immortalization of cells. Constitutive production of these oncoproteins is required for the maintenance of the transformed phenotype of the cells, making these proteins attractive targets for immunotherapeutic strategies against HPVinduced cervical lesions. The therapeutic immunization strategy described in this thesis is based on an alphavirus vector, i.e. Semliki Forest virus vector (SFV). Recombinant SFV expressing a fusion protein of E6 and E7 under control of a translational enhancer (SFV-enhE6,7) is investigated in several preclinical studies using a murine model for HPV-dependent carcinogenesis