Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2003-2-20
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
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
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0340-7004
pubmed:author
pubmed:issnType
Print
pubmed:volume
52
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
97-106
pubmed:dateRevised
2008-11-21
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
pubmed:year
2003
pubmed:articleTitle
A novel adenovirus expressing human 4-1BB ligand enhances antitumor immunity.
pubmed:affiliation
Department of Surgery, Division of Gastroenterological Surgery, Tohoku University Graduate School of Medicine, Japan.
pubmed:publicationType
Journal Article