dc.creator | Lladser, Álvaro | |
dc.creator | Ljungberg, Karl | |
dc.creator | Tufvesson, Helena | |
dc.creator | Tazzari, Marcella | |
dc.creator | Roos, Anna-Karin | |
dc.creator | Quest, Andrew F. G. | |
dc.creator | Kiessling, Rolf | |
dc.date.accessioned | 2010-07-19T20:30:40Z | |
dc.date.available | 2010-07-19T20:30:40Z | |
dc.date.created | 2010-07-19T20:30:40Z | |
dc.date.issued | 2010 | |
dc.identifier | Cancer Immunol Immunother (2010) 59:81–92 | |
dc.identifier | DOI 10.1007/s00262-009-0725-4 | |
dc.identifier | https://repositorio.uchile.cl/handle/2250/128708 | |
dc.description.abstract | Survivin is an intracellular tumor-associated
antigen that is broadly expressed in a large variety of
tumors and also in tumor associated endothelial cells but
mostly absent in diVerentiated tissues. Naked DNA vaccines
targeting survivin have been shown to induce T cell
as well as humoral immune responses in mice. However,
the lack of epitope-speciWc CD8+ T cell detection and modest
tumor protection observed highlight the need for further
improvements to develop eVective survivin DNA vaccination
approaches. Here, the eYcacy of a human survivin
DNA vaccine delivered by intradermal electroporation (EP)
was tested. The CD8+ T cell epitope surv20–28 restricted to
H-2 Db was identiWed based on in-silico epitope prediction
algorithms and binding to MHC class I molecules. Intradermal
DNA EP of mice with a human survivin encoding
plasmid generated CD8+ cytotoxic T lymphocyte (CTL)
responses cross-reactive with the mouse epitope surv20–28,
as determined by intracellular IFN- staining, suggesting
that self-tolerance has been broken. Survivin-speciWc CTLs
displayed an activated eVector phenotype as determined by
CD44 and CD107 up-regulation. Vaccinated mice displayed
speciWc cytotoxic activity against B16 and peptidepulsed
RMA-S cells in vitro as well as against surv20–28
peptide-pulsed target cells in vivo. Importantly, intradermal
EP with a survivin DNA vaccine suppressed angiogenesis
in vivo and elicited protection against highly aggressive
syngeneic B16 melanoma tumor challenge. We conclude
that intradermal EP is an attractive method for delivering a
survivin DNA vaccine that should be explored also in clinical
studies. | |
dc.language | en | |
dc.publisher | Springer-Verlag | |
dc.subject | Survivin | |
dc.title | Intradermal DNA electroporation induces survivin-speciWc CTLs, suppresses angiogenesis and confers protection against mouse melanoma | |
dc.type | Artículo de revista | |