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Therapeutic vaccines against HPV16-associated tumors. Minireview
1Institute of Molecular Genetics; Academy of Sciences of the Czech Republic, Prague, 166 37 Czech Republic. bubenik@img.cas.cz
Abstract:
Human papilloma viruses (HPV) were found to be closely associated with several types of anogenital tumors, particularly with cervical carcinomas (CC). Of more than 100 HPV types characterized until now, 11 have been classified as high-risk types and detected in human tumor tissue by molecular and immunological techniques. Immunological intervention against HPV can be envisaged at two levels, prophylactic and therapeutic. The therapeutic vaccines constructed to counteract tumors which are already developed utilize two nonstructural early proteins coded by HPV, the products of their E6 and E7 oncogenes. These E6/E7 oncoproteins are the only HPV-coded proteins expressed in CC; they are involved in malignant transformation of HPV-infected cells, their presence is necessary for the maintenance of the malignant phenotype of the cells, and their expression correlates with the transforming potential of HPV. Therefore, the E6/E7 oncoproteins are used for the construction of therapeutic vaccines against HPV-associated neoplasms. The purpose of this review is to discuss the results obtained with HPV16 E6/E7 oncoprotein based therapeutic vaccines in animal tumor models, as well as the prospects and limitations of the vaccines.