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Enhancement of dendritic cell-based vaccine potency by anti-apoptotic siRNAs targeting key pro-apoptotic proteins in cytotoxic CD8(+) T cell-mediated cell death

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dc.contributor.authorKim, Jin Hee-
dc.contributor.authorKang, Tae Heung-
dc.contributor.authorNoh, Kyung Hee-
dc.contributor.authorBae, Hyun Cheol-
dc.contributor.authorYoo, Young Do-
dc.contributor.authorKim, Tae Woo-
dc.contributor.authorSeong, Seung-Yong-
dc.contributor.authorKim, Seok-Ho-
dc.date.accessioned2012-06-11T02:43:20Z-
dc.date.available2012-06-11T02:43:20Z-
dc.date.issued2009-01-29-
dc.identifier.citationIMMUNOLOGY LETTERS; Vol.122 1; 58-67ko_KR
dc.identifier.issn0165-2478-
dc.identifier.urihttps://hdl.handle.net/10371/76953-
dc.description.abstractDendritic cells (DCs) have become an important measure for the treatment of malignancies. Current DC preparations, however, generate short-lived DCs because they are subject to cell death from various apoptotic pressures. Antigen-specific CD8(+) cytotoxic T lymphocytes (CTLs) is one of the main obstacles to limit the DC-mediated immune priming since CTLs can recognize the target antigen expressing DCs as target cells and kill the DCs. CTLs secret perforin and serine protease granzymes during CTL killing. Perforin and serine protease granzymes induce the release of a number of mitochondrial pro-apoptotic factors, which are controlled by members of the BCL-2 family, such as BAK, BAX and BIM. FasL linking to Fas on DCs triggers the activation of caspase-8, which eventually leads to mitochondria-mediated apoptosis via truncation of BID. In this study, we tried to enhance the DC priming capacity by prolonging DC survival using anti-apoptotic siRNA targeting these key pro-apoptotic molecules in CTL killing. Human papillomavirus (HPV)-16 E7 antigen presenting DCs that were transfected with these anti-apoptotic siRNAs showed increased resistance to T cell-mediated death, leading to enhanced V-specific CD8(+) T cell activation in vitro and in vivo. Among them, siRNA targeting BIM (siBIM) generated strongest P-specific E7-specific CD8(+)T cell immunity. More importantly, vaccination with E7 presenting DCs transfected with siBIM was capable of generating a marked therapeutic effect in vaccinated mice. Our data indicate that ex vivo manipulation of DCs with siBIM may represent a plausible strategy for enhancing dendritic cell-based vaccine potency.ko_KR
dc.language.isoenko_KR
dc.publisherELSEVIER SCIENCE BVko_KR
dc.subjectDendritic cellko_KR
dc.subjectImmunotherapyko_KR
dc.subjectsiRNAko_KR
dc.subjectBIMko_KR
dc.subjectSig/E7/LAMP-1ko_KR
dc.subjectHPV E7ko_KR
dc.titleEnhancement of dendritic cell-based vaccine potency by anti-apoptotic siRNAs targeting key pro-apoptotic proteins in cytotoxic CD8(+) T cell-mediated cell deathko_KR
dc.typeArticleko_KR
dc.contributor.AlternativeAuthor김진희-
dc.contributor.AlternativeAuthor강태흥-
dc.contributor.AlternativeAuthor노경희-
dc.contributor.AlternativeAuthor배현철-
dc.contributor.AlternativeAuthor김석호-
dc.contributor.AlternativeAuthor유영도-
dc.contributor.AlternativeAuthor성승용-
dc.contributor.AlternativeAuthor김태우-
dc.identifier.doi10.1016/j.imlet.2008.12.006-
dc.citation.journaltitleIMMUNOLOGY LETTERS-
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