Gene Immunotherapy of Cancer: DNA Vaccines against HPV 16

of PhD. Thesis Gene Immunotherapy of Cancer: DNA Vaccines against HPV 16 Mgr. Ingrid Poláková Cervical carcinoma (CC) represents the second most frequent cancer in women, mostly associated with human papillomavirus (HPV) infection. Nowadays, two prophylactic vaccines, protecting against HPV 16 and HPV 18, are licensed. Nevertheless, development of therapeutic vaccines is desirable to eliminate current HPV infections and to treat progressing tumours. Suitable targets for vaccination are viral E6 and E7 oncoproteins. Since its discovery, DNA vaccination has become an effective strategy for development of vaccines against cancer including CC. Unfortunately, the immunogenicity of DNA vaccines in large animals and particularly in humans is low. Therefore, several ongoing studies are focused on strategies enhancing the efficacy and safety of DNA vaccines. In this work, the immunogenicity of DNA vaccines against HPV 16 delivered by a gene gun was evaluated after the fusion of the E7 and E6 genes with GUS. The increased steady-state level of the E7GGG.GUS deletion mutants and the GUS.E7GGG fusion protein enhanced the production of E7-specific antibodies after immunisation with these vaccines but did not improve the CTL response. Joining of the signal sequence with GUS.E7GGG led to ER-localisation of the..