PuSH - Publikationsserver des Helmholtz Zentrums München: Anti-tumor CD8⁺ T cell immunity elicited by HIV-1-based virus-like particles incorporating HPV-16 E7 protein.

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di Bonito, P.* ; Grasso, F.* ; Mochi, S.* ; Petrone, L.* ; Fanales-Belasio, E.* ; Mei, A.* ; Cesolini, A.* ; Laconi, G.* ; Conrad, H.* ; Bernhard, H.* ; Dembek, C.J. ; Cosma, A. ; Santini, S.M.* ; Lapenta, C.* ; Donati, S.* ; Muratori, C.* ; Giorgi, C.* ; Federico, M.*

Anti-tumor CD8⁺ T cell immunity elicited by HIV-1-based virus-like particles incorporating HPV-16 E7 protein.

Virology 395, 45-55 (2009)

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Here we report a novel strategy for the induction of CD8(+) T cell adaptive immune response against viral and tumor antigens. This approach relies on high levels of incorporation in HIV-1 VLPs of a mutant of HIV-1 Nef (Nef(mut)) which can act as anchoring element for foreign proteins. By in vitro assay, we found that VLP-associated Nef(mut) is efficiently cross-presented by antigen presenting cells. Inoculation in mice of VLPs incorporating the HPV-16 E7 protein fused to Nef(mut) led to an anti-E7 CD8(+) T cell response much stronger than that elicited by E7 recombinant protein inoculated with incomplete Freund's adjuvant and correlating with well-detectable anti-E7 CTL activity. Most relevantly, mice immunized with Nef(mut)-E7 VLPs developed a protective immune response against tumors induced by E7 expressing tumor cells. These results make Nef(mut) VLPs a promising candidate for new vaccine strategies focused on the induction of CD8(+) T cell immunity.

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