Antitumor activity of DNA vaccines based on the human papillomavirus-16 E7 protein genetically fused to a plant virus coat protein

TitleAntitumor activity of DNA vaccines based on the human papillomavirus-16 E7 protein genetically fused to a plant virus coat protein
Publication TypeArticolo su Rivista peer-reviewed
Year of Publication2008
AuthorsMassa, Silvia, Simeone P., Muller A., Benvenuto Eugenio, Venuti A., and Franconi Rosella
JournalHuman Gene Therapy
Keywordsanimal experiment, animal model, Animals, Antibodies, Antibody Formation, antibody response, antineoplastic activity, article, C57BL 6 mouse, cancer inhibition, Cancer Vaccines, Capsid Proteins, Cell Line, cell strain HEK293, Cellular, coat protein, controlled study, cytokine release, DNA, DNA immunization, DNA vaccine, drug potency, enzyme linked immunospot assay, Female, gamma interferon, Gene expression, gene fusion, genetic transfection, human, human cell, Human papillomavirus, Human papillomavirus - 16, Human papillomavirus type 16, hybrid protein, Immunity, immunofluorescence microscopy, Inbred C57BL, Mammalia, Mice, mouse, Mus, nonhuman, Oncogene Proteins, plasmid complementary DNA coat protein, plasmid complementary DNA E7GGG coat protein, plasmid complementary DNA E7GGG protein, plasmid DNA, Potato virus X, Potexvirus, Proteasome Endopeptidase Complex, proteasome inhibitor, protein E7, protein expression, Recombinant Fusion Proteins, Tumor, uterine cervix carcinoma, Vaccines, Viral

DNA vaccination represents an attractive strategy for cancer immunotherapy combining vaccine stability, cost-effectiveness, and safety. However, a major problem of genetic vaccination is the limited potency, due to intrinsic lack of amplifying and spreading abilities in vivo and to the suboptimal intracellular processing/presentation of tumor antigens. We explored the therapeutic antitumor potency of DNA vaccines based on a mutated, nontransforming form of the E7 gene (E7GGG gene) of human papilloma virus 16 (HPV-16) fused, with or without a linker, to the potato virus X (PVX) coat protein sequence (PVX-CP). Transfection of mammalian cells demonstrated expression of the E7GGG protein, while the fusion proteins were detected only in the presence of proteasome inhibitors, suggesting increased instability and faster degradation via the proteasome. The DNA fusion vaccines, administered intramuscularly to C57BL/6 mice after challenging with a tumorigenic dose of E7-expressing TC-1 cells, inhibited the growth of tumors in vivo better than the E7GGG gene alone and induced both humoral and cell-mediated immune responses. Therefore, fusion of the HPV-16 E7GGG gene with a plant virus coat protein gene might be a valid strategy to induce antitumor immunity in a safe setting by a novel genetic vaccine targeting cervical carcinoma. © 2008 Mary Ann Liebert, Inc.


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