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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2005-4-21
pubmed:abstractText
Antiangiogenic immunotherapy benefits from targeting antigens expressed on genetically stable endothelial cells and represents a novel modality for cancer treatment. Vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2, also known as flk1 in mouse) mediated VEGF signaling is the key rate-limiting step in angiogenesis. Blockade of the flk1 signaling pathway can significantly inhibit tumor cell-induced angiogenesis and lead to inhibition of tumor metastasis. Interferon-gamma (IFN-gamma) is a pleiotropic cytokine, which plays an important role in cell-mediated immunity. In this study, we tested the hypothesis that immunization of mice with soluble flk1 (sflk1) and IFN-gamma fusion gene-transfected dendritic cells (DC-sflk1-IFN-gamma) would induce a potent CTL response to flk1, leading to an inhibition of tumor-induced angiogenesis and metastasis. Our data show that immunization of mice with sflk1 gene-modified DC (DC-sflk1) could induce a CTL response to flk1, leading to profound inhibition of tumor-cell-induced angiogenesis and metastasis. However, more striking antimetastatic effects were achieved through induction of enhanced CTL response to flk1 and augmented inhibition of angiogenesis when mice were immunized with DC-sflk1-IFN-gamma. In vivo T-cell subset depletion experiments showed that CD8(+) T cells were mainly responsible for this antimetastatic effect. Our data extend the notion that DC-based active antiangiogenic immunotherapy is an effective modality for cancer treatment, and show that the antitumor efficacy of this strategy can be improved by combination with DC-based cytokine immunotherapy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0969-7128
pubmed:author
pubmed:issnType
Print
pubmed:volume
12
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
742-50
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:15729371-Animals, pubmed-meshheading:15729371-CD8-Positive T-Lymphocytes, pubmed-meshheading:15729371-Cancer Vaccines, pubmed-meshheading:15729371-Carcinoma, Lewis Lung, pubmed-meshheading:15729371-Cytotoxicity, Immunologic, pubmed-meshheading:15729371-Dendritic Cells, pubmed-meshheading:15729371-Electroporation, pubmed-meshheading:15729371-Female, pubmed-meshheading:15729371-Immunity, Cellular, pubmed-meshheading:15729371-Immunization, pubmed-meshheading:15729371-Interferon-gamma, pubmed-meshheading:15729371-Melanoma, Experimental, pubmed-meshheading:15729371-Mice, pubmed-meshheading:15729371-Mice, Inbred C57BL, pubmed-meshheading:15729371-Neoplasm Metastasis, pubmed-meshheading:15729371-Neoplasms, Experimental, pubmed-meshheading:15729371-Neovascularization, Pathologic, pubmed-meshheading:15729371-Plasmids, pubmed-meshheading:15729371-Transfection, pubmed-meshheading:15729371-Vaccines, DNA, pubmed-meshheading:15729371-Vascular Endothelial Growth Factor Receptor-2
pubmed:year
2005
pubmed:articleTitle
Enhanced antimetastatic effect of fetal liver kinase 1 extracellular domain and interferon-gamma fusion gene-modified dendritic cell vaccination.
pubmed:affiliation
Institute of Immunology, Zhejiang University, Hangzhou, People's Republic of China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't