rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2003-2-20
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pubmed:abstractText |
4-1BB ligand (4-1BBL), a member of the tumor necrosis factor (TNF) superfamily, interacts with 4-1BB (CDw137) expressed on activated T cells and delivers a costimulatory signal for T cell activation and growth. Various studies have demonstrated a role for murine 4-1BB in immune function, but relatively few investigations of human 4-1BB have been conducted. Here we report on the construction of a recombinant E1/E3-deleted adenovirus encoding human 4-1BBL (Ad4-1BBL) and its stimulation of antitumor immunity. Ad4-1BBL was able to efficiently infect several human adenocarcinoma cell lines and induce 4-1BBL expression on the cell surface within 24 h, this enhancing the antitumor activity not only of lymphokine-activated killer cells with a T cell phenotype (T-LAK) but also naive peripheral blood mononuclear cells (PBMC). This antitumor activity with T-LAK cells was further enhanced by addition of bispecific antibody (BsAb; anti-MUC1xanti-CD3). Cocultivation of Ad4-1BBL-infected tumor cells with either T-LAK cells or PBMC resulted in significant elevation of interferon-gamma (IFN-gamma), interleukin-2 (IL-2), and granulocyte-macrophage colony-stimulating factor (GM-CSF) production. Furthermore, remarkable tumor growth inhibition was observed in cholangiocarcinoma-grafted severe combined immunodeficient (SCID) mice to which Ad4-1BBL and T-LAK cells were administered when tumor size exceeded 5 mm in diameter. These results provide strong evidence in support of the efficacy of adenovirally delivered 4-1BBL for genetic immunotherapy of cancer.
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pubmed:language |
eng
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pubmed:journal |
|
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/4-1BB Ligand,
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Bispecific,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD137,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD3,
http://linkedlifedata.com/resource/pubmed/chemical/Granulocyte-Macrophage...,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-2,
http://linkedlifedata.com/resource/pubmed/chemical/Mucin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Nerve Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Tumor Necrosis Factor,
http://linkedlifedata.com/resource/pubmed/chemical/TNFRSF9 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/TNFSF9 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Tnfrsf9 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Tnfsf9 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0340-7004
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pubmed:author |
pubmed-author:AsanoRyutaroR,
pubmed-author:HayashiHirokiH,
pubmed-author:KatayoseYuY,
pubmed-author:KodamaHideakiH,
pubmed-author:KudoToshioT,
pubmed-author:MatsunoSeikiS,
pubmed-author:SuzukiMasanoriM,
pubmed-author:TakemuraShin-ichiS,
pubmed-author:UnnoMichiakiM,
pubmed-author:YamamotoKuniharuK,
pubmed-author:YoshidaHiroshiH
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pubmed:issnType |
Print
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pubmed:volume |
52
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
97-106
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:12594573-4-1BB Ligand,
pubmed-meshheading:12594573-Adenoviridae,
pubmed-meshheading:12594573-Animals,
pubmed-meshheading:12594573-Antibodies, Bispecific,
pubmed-meshheading:12594573-Antigens, CD,
pubmed-meshheading:12594573-Antigens, CD137,
pubmed-meshheading:12594573-Antigens, CD3,
pubmed-meshheading:12594573-Bile Duct Neoplasms,
pubmed-meshheading:12594573-Bile Ducts, Intrahepatic,
pubmed-meshheading:12594573-Cholangiocarcinoma,
pubmed-meshheading:12594573-Gene Therapy,
pubmed-meshheading:12594573-Granulocyte-Macrophage Colony-Stimulating Factor,
pubmed-meshheading:12594573-Humans,
pubmed-meshheading:12594573-Interferon-gamma,
pubmed-meshheading:12594573-Interleukin-2,
pubmed-meshheading:12594573-Killer Cells, Lymphokine-Activated,
pubmed-meshheading:12594573-Mice,
pubmed-meshheading:12594573-Mice, SCID,
pubmed-meshheading:12594573-Mucin-1,
pubmed-meshheading:12594573-Neoplasm Transplantation,
pubmed-meshheading:12594573-Neoplasms, Experimental,
pubmed-meshheading:12594573-Receptors, Nerve Growth Factor,
pubmed-meshheading:12594573-Receptors, Tumor Necrosis Factor,
pubmed-meshheading:12594573-Tumor Cells, Cultured,
pubmed-meshheading:12594573-Tumor Necrosis Factor-alpha
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pubmed:year |
2003
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pubmed:articleTitle |
A novel adenovirus expressing human 4-1BB ligand enhances antitumor immunity.
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pubmed:affiliation |
Department of Surgery, Division of Gastroenterological Surgery, Tohoku University Graduate School of Medicine, Japan.
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pubmed:publicationType |
Journal Article
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