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Factors involved in the maturation of murine dendritic cells transduced with adenoviral vector variants.
- Source :
-
Virology [Virology] 2008 May 10; Vol. 374 (2), pp. 411-20. Date of Electronic Publication: 2008 Feb 12. - Publication Year :
- 2008
-
Abstract
- Adenoviral vector (Ad)-mediated gene transfer is an attractive method for manipulating the immunostimulatory properties of dendritic cells (DCs) for cancer immunotherapy. DCs treated with Ad have phenotype alterations (maturation) that facilitate T cell sensitization. We investigated the mechanisms of DC maturation with Ad transduction. Expression levels of a maturation marker (CD40) on DCs treated with conventional Ad, fiber-modified Ads (AdRGD, AdF35, AdF35DeltaRGD), or a different serotype Ad (Ad35) were correlated with their transduction efficacy. The alphav-integrin directional Ad, AdRGD, exhibited the most potent ability to enhance both foreign gene expression and CD40 expression, and induced secretion of interleukin-12, tumor necrosis factor-alpha, and interferon-alpha in DCs. The presence of a foreign gene expression cassette in AdRGD was not necessary for DC maturation. Maturation of DCs treated with AdRGD was suppressed by destruction of the Ad genome, inhibition of endocytosis, or endosome acidification, whereas proteasome inhibition increased CD40 expression levels on DCs. Moreover, inhibition of alphav-integrin signal transduction and blockade of cytokine secretion affected the maturation of DCs treated with AdRGD only slightly or not at all, respectively. Thus, our data provide evidence that Ad-induced DC maturation is due to Ad invasion of the DCs, followed by nuclear transport of the Ad genome, and not to the expression of foreign genes.
- Subjects :
- Animals
CD40 Antigens genetics
CD40 Antigens metabolism
Female
Green Fluorescent Proteins genetics
Green Fluorescent Proteins metabolism
Mice
Mice, Inbred BALB C
Viral Proteins genetics
Viral Proteins metabolism
Adenoviridae classification
Adenoviridae genetics
Adenoviridae pathogenicity
Cell Differentiation
Dendritic Cells cytology
Dendritic Cells virology
Genetic Vectors
Transduction, Genetic
Subjects
Details
- Language :
- English
- ISSN :
- 0042-6822
- Volume :
- 374
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Virology
- Publication Type :
- Academic Journal
- Accession number :
- 18272197
- Full Text :
- https://doi.org/10.1016/j.virol.2007.12.043