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000128915 037__ $$aDKFZ-2017-04928
000128915 041__ $$aeng
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000128915 1001_ $$00000-0002-2866-3901$$aKnippertz, Ilka$$b0
000128915 245__ $$aTranscriptional Targeting of Mature Dendritic Cells with Adenoviral Vectors via a Modular Promoter System for Antigen Expression and Functional Manipulation.
000128915 260__ $$aNew York, NY$$bHindawi$$c2016
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000128915 520__ $$aTo specifically target dendritic cells (DCs) to simultaneously express different therapeutic transgenes for inducing immune responses against tumors, we used a combined promoter system of adenoviral vectors. We selected a 216 bp short Hsp70B' core promoter induced by a mutated, constitutively active heat shock factor (mHSF) 1 to drive strong gene expression of therapeutic transgenes MelanA, BclxL, and IL-12p70 in HeLa cells, as well as in mature DCs (mDCs). As this involves overexpressing mHSF1, we first evaluated the resulting effects on DCs regarding upregulation of heat shock proteins and maturation markers, toxicity, cytokine profile, and capacity to induce antigen-specific CD8(+) T cells. Second, we generated the two-vector-based 'modular promoter' system, where one vector contains the mHSF1 under the control of the human CD83 promoter, which is specifically active only in DCs and after maturation. mHSF1, in turn, activates the Hsp70B' core promotor-driven expression of transgenes MelanA and IL-12p70 in the DC-like cell line XS52 and in human mature and hence immunogenic DCs, but not in tolerogenic immature DCs. These in vitro experiments provide the basis for an in vivo targeting of mature DCs for the expression of multiple transgenes. Therefore, this modular promoter system represents a promising tool for future DC-based immunotherapies in vivo.
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000128915 650_7 $$2NLM Chemicals$$aAntigens, CD
000128915 650_7 $$2NLM Chemicals$$aBCL2L1 protein, human
000128915 650_7 $$2NLM Chemicals$$aCD83 antigen
000128915 650_7 $$2NLM Chemicals$$aCytokines
000128915 650_7 $$2NLM Chemicals$$aDNA-Binding Proteins
000128915 650_7 $$2NLM Chemicals$$aImmunoglobulins
000128915 650_7 $$2NLM Chemicals$$aMART-1 Antigen
000128915 650_7 $$2NLM Chemicals$$aMembrane Glycoproteins
000128915 650_7 $$2NLM Chemicals$$aTranscription Factors
000128915 650_7 $$2NLM Chemicals$$abcl-X Protein
000128915 650_7 $$2NLM Chemicals$$aheat shock transcription factor
000128915 650_7 $$0187348-17-0$$2NLM Chemicals$$aInterleukin-12
000128915 7001_ $$aDeinzer, Andrea$$b1
000128915 7001_ $$00000-0002-3478-0741$$aDörrie, Jan$$b2
000128915 7001_ $$00000-0001-8236-9298$$aSchaft, Niels$$b3
000128915 7001_ $$00000-0002-1225-2593$$aNettelbeck, Dirk M$$b4
000128915 7001_ $$00000-0001-7187-6729$$aSteinkasserer, Alexander$$b5
000128915 773__ $$0PERI:(DE-600)2817541-4$$a10.1155/2016/6078473$$gVol. 2016, p. 1 - 17$$p1 - 17$$tJournal of Immunology Research$$v2016$$x2314-7156$$y2016
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