Source:http://linkedlifedata.com/resource/pubmed/id/19848448
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
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| pubmed:dateCreated |
2009-11-13
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| pubmed:abstractText |
Toll-like receptor (TLR)-mediated signaling is proposed as an immunotherapeutic target against tumorigenesis. Natural killer (NK) cells play a critical role in host defense against tumors. Specifically, formation of tumor metastasis in various organs can be suppressed by the local activity of NK cells. In this study, we present a novel TLR7 agonist (termed SC-1) that induces pro-inflammatory cytokines in human blood cells, activates NK cell function, and is highly efficient in preventing lung metastases in a pulmonary metastatic Renca model. Furthermore, a second compound (termed SC-2), acting as dual-specific TLR7 and TLR8 agonist, was evaluated with respect to its immunostimulatory and NK cell-activating capacities. The release of pro-inflammatory cytokines was shown to be even more pronounced with this compound. Additional experiments showed a significant up-regulation of activation marker CD69 on NK cells and increased cytolytic activity of peripheral blood cells compared to the effect of a monospecific TLR7 agonist SC-1. Normally, TLR7 and TLR8 are expressed on different immune cell subpopulations. TLR7 expression on antigen-presenting cells is detected in plasmacytoid dendritic cells, CD34+-derived dendritic cells, and B-cells, whereas TLR8 is mainly expressed on cells of the myeloid lineage, such as monocytes, macrophages, and myeloid dendritic cells. Therefore, a compound that activates both TLR7 and TLR8 would result in a highly efficient immune system activation and may give rise to an enhanced anti-tumor activity in vivo compared to that elicited by a monospecific TLR7 agonist.
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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/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Differentiation...,
http://linkedlifedata.com/resource/pubmed/chemical/CD69 antigen,
http://linkedlifedata.com/resource/pubmed/chemical/Lectins, C-Type,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/SC-1 monoclonal antibody,
http://linkedlifedata.com/resource/pubmed/chemical/Tlr7 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptor 7,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptor 8
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| pubmed:status |
MEDLINE
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| pubmed:month |
Dec
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| pubmed:issn |
1547-6901
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:volume |
6
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
257-65
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| pubmed:dateRevised |
2010-11-18
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| pubmed:meshHeading |
pubmed-meshheading:19848448-Animals,
pubmed-meshheading:19848448-Antibodies, Monoclonal,
pubmed-meshheading:19848448-Antigens, CD,
pubmed-meshheading:19848448-Antigens, Differentiation, T-Lymphocyte,
pubmed-meshheading:19848448-Cell Death,
pubmed-meshheading:19848448-Cell Line,
pubmed-meshheading:19848448-Dendritic Cells,
pubmed-meshheading:19848448-Drug Screening Assays, Antitumor,
pubmed-meshheading:19848448-Female,
pubmed-meshheading:19848448-Humans,
pubmed-meshheading:19848448-Immunotherapy,
pubmed-meshheading:19848448-Killer Cells, Natural,
pubmed-meshheading:19848448-Lectins, C-Type,
pubmed-meshheading:19848448-Lung Neoplasms,
pubmed-meshheading:19848448-Lymphocyte Activation,
pubmed-meshheading:19848448-Membrane Glycoproteins,
pubmed-meshheading:19848448-Mice,
pubmed-meshheading:19848448-Mice, Inbred BALB C,
pubmed-meshheading:19848448-Toll-Like Receptor 7,
pubmed-meshheading:19848448-Toll-Like Receptor 8
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| pubmed:year |
2009
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| pubmed:articleTitle |
Cancer immunotherapeutic potential of novel small molecule TLR7 and TLR8 agonists.
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| pubmed:affiliation |
svetlana.hamm@4sc.com
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| pubmed:publicationType |
Journal Article
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