Antitumor activity of DNA vaccines based on the human papillomavirus-16 E7 protein genetically fused to a plant virus coat protein.
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.
Massa
Silvia
S
Biotechnologies, Agro-Industry and Health Protection Department, Italian National Agency for New Technologies, Energy, and the Environment, ENEA C.R. Casaccia, 00123 Rome, Italy.
Simeone
Paola
P
Muller
Antonio
A
Benvenuto
Eugenio
E
Venuti
Aldo
A
Franconi
Rosella
R
D000818:Animals; D000906:Antibodies / Q000276:immunology; D000917:Antibody Formation; D019496:Cancer Vaccines / Q000276:immunology*; D036022:Capsid Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D015870:Gene Expression; D007111:Immunity, Cellular; D051379:Mice; D008810:Mice, Inbred C57BL; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology*; D050725:Papillomavirus E7 Proteins; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology*; D019444:Vaccines, DNA / Q000276:immunology*
D000906:Antibodies; D019496:Cancer Vaccines; D036022:Capsid Proteins; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; C058750:coat protein, Potato virus X; C059731:oncogene protein E7, Human papillomavirus type 16; D046988:Proteasome Endopeptidase Complex