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Gene Ther. 2008 Feb;15(3):203-13. Epub 2007 Nov 8.

Gene transfer of CD40-ligand to dendritic cells stimulates interferon-gamma production to induce growth arrest and apoptosis of tumor cells.

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1
Department of Molecular Medicine, Sapporo Medical University, Sapporo, Japan.

Abstract

In this study, we present evidence that gene transfer of the CD40-ligand (CD154) into human immature dendritic cells (DC) imparts direct antitumor effects on tumor cells. DC infected with adenovirus directed to express human CD154 on the cell surface (CD154-DC) elicited significantly higher levels of immune accessory molecules commonly found on mature DC. We found that co-cultivation with a human squamous cell carcinoma cell line (OSC-70) with CD154-DC significantly inhibited cell growth. We further demonstrate that OSC-70 cells stimulated with CD154-DC were more susceptible to apoptosis via TNF-related apoptosis inducing ligand (TRAIL). Importantly, tumor cells co-cultured with CD154-DC in transwell plates expressed upregulated cell surface TRAIL-R2. CD154-DC produced higher levels of interferon (IFN)-gamma, IL-12p70 and soluble CD154, but the ability of CD154-DC to inhibit tumor cell growth was significantly abrogated by a neutralizing antibody to IFN-gamma, indicating that this was mainly mediated by IFN-gamma. Furthermore, intratumoral injection of CD154-DC significantly suppressed OSC-70 tumor growth in a xenograft model. Overall, these results reveal that CD154-DC have potential as an anti-cancer therapy by producing IFN-gamma to arrest adjacent tumor cell growth and increase the susceptibility of apoptosis via TRAIL.

PMID:
17989706
DOI:
10.1038/sj.gt.3303056
[Indexed for MEDLINE]
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