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

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

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

K Tomihara,K Kato,Y Masuta,K Nakamura,H Uchida,K Sasaki,T Tanaka,J Huang,H Hiratsuka,H Hamada,K Tomihara,K Kato,Y Masuta,K Nakamura,H Uchida,K Sasaki,T Tanaka,J Huang,H Hiratsuka,H Hamada,

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.Gene Therapy (2008) 15, 203-213; doi:10.1038/sj.gt.3303056; published online 8 November 2007.

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

K Tomihara,K Kato,Y Masuta,K Nakamura,H Uchida,K Sasaki,T Tanaka,J Huang,H Hiratsuka,H Hamada,K Tomihara,K Kato,Y Masuta,K Nakamura,H Uchida,K Sasaki,T Tanaka,J Huang,H Hiratsuka,H Hamada,

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

PUBLICATION TYPE: Journal Article

Journal: Gene therapy

VOLUME: 15

Page Numbers: 203-13

Journal Abbreviation: Gene Ther.

ISSN: 0969-7128

DAY: 8

MONTH: 11

YEAR: 2007

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

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LANGUAGE: eng

NlmUniqueID: 9421525

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

AFFILIATION: [1] 1Department of Molecular Medicine, Sapporo Medical University, Sapporo, Japan [2] 2Department of Oral Surgery, Sapporo Medical University, Sapporo, Japan.

Country: England

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MEDLINETA: Gene Ther

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