Artículo de revista
Intradermal DNA electroporation induces survivin-speciWc CTLs, suppresses angiogenesis and confers protection against mouse melanoma
Fecha
2010Registro en:
Cancer Immunol Immunother (2010) 59:81–92
DOI 10.1007/s00262-009-0725-4
Autor
Lladser, Álvaro
Ljungberg, Karl
Tufvesson, Helena
Tazzari, Marcella
Roos, Anna-Karin
Quest, Andrew F. G.
Kiessling, Rolf
Institución
Resumen
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.