|Title||A prime/boost strategy by DNA/fowlpox recombinants expressing a mutant E7 protein for the immunotherapy of HPV-associated cancers|
|Publication Type||Articolo su Rivista peer-reviewed|
|Year of Publication||2012|
|Authors||Radaelli, A., C. Morghen De Giuli, Zanotto C., Pacchioni S., Bissa M., Franconi Rosella, Massa Silvia, Paolini F., Muller A., and Venuti A.|
|Keywords||animal cell, animal experiment, animal model, Animals, Antibody, antibody response, article, cancer immunotherapy, Cancer Vaccines, Cell Line, Cellular, DNA, DNA protein E7 glycylglycylglycine, DNA vaccine, drug efficacy, Female, Fowlpox virus, Fowlpox virus protein E7 glycylglycylglycine, Gene expression, heterologous expression, Human papillomavirus, Human papillomavirus 16, Human papillomavirus type 16, Humans, Humoral, Immunity, Immunization Schedule, immunotherapy, Mice, mouse, Mus, Mutant Proteins, Neoplasm, Neoplasms, nonhuman, Papillomavirus E7 Proteins, Papillomavirus Vaccines, Plasmids, priority journal, protein E7, protein E7 antibody, protein expression, sequence homology, Transgenes, unclassified drug, Vaccines, virus recombinant, Wart virus vaccine|
Development of effective therapeutic vaccines against human papilloma virus (HPV) infections remains a priority, considering the high number of new cases of cervical cancer each year by high-risk HPVs, in particular by HPV-16. Vaccines expressing the E7 oncoprotein, which is detectable in all HPV-positive pre-cancerous and cancer cells, might clear already established tumors and support the treatment of HPV-related lesions. In this study, DNA or fowlpox virus recombinants expressing the harmless variant E7GGG of the HPV-16 E7 oncoprotein (DNAE7GGG and FPE7GGG) were generated. Two immunization regimens were tested in a pre-clinical mouse model by homologous (FP/FP) or heterologous (DNA/FP) prime-boost protocols to evaluate the immune response and therapeutic efficacy of the proposed HPV-16 vaccine. Low levels of anti-E7-specific antibodies were elicited after immunization, and in vivo experiments resulted in a higher number of tumor-free mice after the heterologous immunization. These results establish a preliminary indication for therapy of HPV-related tumors by the combined use of DNA and avipox recombinants, which might represent safer immunogens than vaccinia-based vaccines. © 2012 Elsevier B.V.
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