Animal models for development of therapeutic HPV16 vaccines (Review)

In several types of human tumours a close association with oncogenic viruses has been established. Animal models mimicking these tumours with regard to their aetiology and expression of virus-related molecules have been developed. The rationale for development of the animal models was to create experimental systems allowing us to compare the efficacy of immunological and gene therapy protocols, with the final aim to optimize these therapeutic procedures prior to clinical trials. Anogenital carcinomas and particularly cervical carcinomas (CC) represent one of the aforementioned human oncogenic virus-associated tumour types. High-risk human papilloma viruses (HPV), particularly HPV16, 18, 31, 33, 45, and 56, are associated with nearly one hundred percent of CC. The only HPV proteins expressed in CC and representing the potential therapeutic targets are the non-structural viral gene products E6 and E7. The E6/E7 oncoproteins inactivate p53 and pRb tumour suppressor genes, they are required for maintenance of the malignant phenotype and their expression correlates with the transforming potential of HPV. Since the various HPV types do not cross-react with regard to the induction of both, humoral and cell-mediated immunity, the research of therapeutic vaccines is focused primarily on the HPV type 16, which is expressed in the majority, nearly 60%, of human squamous CC, and on the HPV16 E6/E7 oncogene products, which represent a target of choice for the therapeutic vaccination. The purpose of this review is to discuss the animal models of HPV-associated human tumours and the results obtained in these models with therapeutic vaccination against HPV-associated tumours. The prospects and limitations of the vaccination against HPV-associated tumours are also addressed.