Targeting dendritic cells with antigen via dendritic cell-associated promoters

The induction of tumor-specific immune responses is largely dependent on the ability of dendritic cells (DCs) to present tumor-associated antigens to T lymphocytes. Therefore, we investigated the use of DC-associated promoter-driven genetic vaccines to specifically target DC in vivo . Restricted exp...

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Bibliographic Details
Published in:	Cancer gene therapy Vol. 19; no. 5; pp. 303 - 311
Main Authors:	Moulin, V, Morgan, M E, Eleveld-Trancikova, D, Haanen, J B A G, Wielders, E, Looman, M W G, Janssen, R A J, Figdor, C G, Jansen, B J H, Adema, G J
Format:	Journal Article
Language:	English
Published:	New York Nature Publishing Group US 01-05-2012 Nature Publishing Group
Subjects:	631/250/2504/133 631/61/51/201 Animal models Animals Antigen (tumor-associated) Antigen Presentation Antigens Antigens, Neoplasm - immunology Antigens, Neoplasm - metabolism Biomedical and Life Sciences Biomedicine CD11c antigen CD11c Antigen - genetics CD11c Antigen - immunology CD4 antigen CD8 antigen Cell Adhesion Molecules - genetics Cell Adhesion Molecules - immunology Cell proliferation DC-SIGN protein DC-STAMP protein Dendritic cells Dendritic Cells - immunology Electroporation Female Gene Expression Gene Therapy Green fluorescent protein Immune response Immunotherapy, Adoptive - methods Lectins, C-Type - genetics Lectins, C-Type - immunology Lymphocytes T Melanoma, Experimental - immunology Melanoma, Experimental - therapy Membrane Proteins - genetics Membrane Proteins - immunology Mice Mice, Inbred C57BL Mice, Transgenic Nerve Tissue Proteins - genetics Nerve Tissue Proteins - immunology NIH 3T3 Cells original-article Ovalbumin Physiological aspects Promoter Regions, Genetic Promoters Promoters (Genetics) Receptors, Cell Surface - genetics Receptors, Cell Surface - immunology T-Lymphocytes - immunology Transfection Vaccines Vaccines, DNA - genetics Vaccines, DNA - immunology Netherlands tattoo DNA vaccination DC-specific promoter dendritic cell
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Summary:	The induction of tumor-specific immune responses is largely dependent on the ability of dendritic cells (DCs) to present tumor-associated antigens to T lymphocytes. Therefore, we investigated the use of DC-associated promoter-driven genetic vaccines to specifically target DC in vivo . Restricted expression of vaccine-encoding genes in DC should enhance specificity and improves their safety for clinical applications. Hereto, 3–5 kb upstream sequences of the murine genes encoding CD11c, DC-SIGN, DC-STAMP and Langerin were isolated, characterized and subcloned into enhanced green fluorescent protein (EGFP) reporter constructs. Upon electroporation, EGFP was expressed in DC cell lines, but not in other cell lines, confirming DC-restricted promoter activity. When these promoters were cloned into a construct upstream of the gene for ovalbumin (OVA), it appeared that DC-STAMP promoter-driven expression of OVA (pDCSTAMP/OVA) in DC yielded the most efficient OVA-specific CD4+ and CD8+ T-cell responses in vitro. Administration of pDC-STAMP/OVA in vivo , using the tattoo gun vaccination system, evoked specific immune responses as evidenced in a mouse tumor model. Adoptively transferred pDC-STAMP/OVA-transfected DCs induced strong CD8+ T-cell proliferation in vivo. These experiments demonstrate that our DC-directed promoter constructs are potential tools to restrict antigen expression in DC and could be implemented to modulate DC function by the introduction of relevant proteins.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1
ISSN:	0929-1903 1476-5500
DOI:	10.1038/cgt.2012.2