Intradermal DNA electroporation induces survivin-specific CTLs, suppresses angiogenesis and confers protection against mouse melanoma Export

@article{citeulike:4934430, abstract = {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 differentiated 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-specific CD8+ T cell detection and modest tumor protection observed highlight the need for further improvements to develop effective survivin DNA vaccination approaches. Here, the efficacy 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 identified 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-γ staining, suggesting that self-tolerance has been broken. Survivin-specific CTLs displayed an activated effector phenotype as determined by CD44 and CD107 up-regulation. Vaccinated mice displayed specific cytotoxic activity against B16 and peptide-pulsed 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.}, author = {Lladser, Alvaro and Ljungberg, Karl and Tufvesson, Helena and Tazzari, Marcella and Roos, Anna-Karin and Quest, Andrew and Kiessling, Rolf}, citeulike-article-id = {4934430}, citeulike-linkout-0 = {http://dx.doi.org/10.1007/s00262-009-0725-4}, citeulike-linkout-1 = {http://www.springerlink.com/content/t47874wr63468906}, day = {1}, doi = {10.1007/s00262-009-0725-4}, journal = {Cancer Immunology, Immunotherapy}, keywords = {angiogenesis, dual-targeting, survivin, tumor-antigen}, month = {January}, number = {1}, pages = {81--92}, posted-at = {2009-11-15 05:02:46}, priority = {2}, title = {Intradermal DNA electroporation induces survivin-specific CTLs, suppresses angiogenesis and confers protection against mouse melanoma}, url = {http://dx.doi.org/10.1007/s00262-009-0725-4}, volume = {59}, year = {2010} }

TY - JOUR ID - citeulike:4934430 L3 - citeulike-article-id:4934430 N2 - 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 differentiated 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-specific CD8+ T cell detection and modest tumor protection observed highlight the need for further improvements to develop effective survivin DNA vaccination approaches. Here, the efficacy 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 identified 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-γ staining, suggesting that self-tolerance has been broken. Survivin-specific CTLs displayed an activated effector phenotype as determined by CD44 and CD107 up-regulation. Vaccinated mice displayed specific cytotoxic activity against B16 and peptide-pulsed 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. IS - 1 JF - Cancer Immunology, Immunotherapy EP - 92 TI - Intradermal DNA electroporation induces survivin-specific CTLs, suppresses angiogenesis and confers protection against mouse melanoma VL - 59 SP - 81 KW - angiogenesis KW - dual-targeting KW - survivin KW - tumor-antigen AU - Lladser, Alvaro AU - Ljungberg, Karl AU - Tufvesson, Helena AU - Tazzari, Marcella AU - Roos, Anna-Karin AU - Quest, Andrew AU - Kiessling, Rolf PY - 2010/01/01/ UR - http://dx.doi.org/10.1007/s00262-009-0725-4 ER -