Source:http://linkedlifedata.com/resource/pubmed/id/20842106
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
11
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| pubmed:dateCreated |
2010-11-2
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| pubmed:abstractText |
Adoptive transfer of antigen-specific cytotoxic T lymphocytes has shown promise for the therapy of cancer. However, tumor-specific T cells are susceptible to diverse inhibitory signals from the tumor microenvironment. The Akt/protein kinase B plays a central role in T-cell proliferation, function, and survival and we hypothesized that expression of constitutively active Akt (caAkt) in T cells could provide resistance to many of these tumor-associated inhibitory mechanisms. caAkt expression in activated human T cells increased proliferation and cytokine production, a likely result of their sustained expression of nuclear factor-?B (NF-?B) and provided resistance to apoptosis by upregulating antiapoptotic molecules. caAkt expressing T cells (caAkt-T-cells) were also relatively resistant to suppression by and conversion into regulatory T cells (Tregs). These characteristics provided a survival advantage to T cells cocultured with tumor cells in vitro; CD3/28-stimulated T cells expressing a chimeric antigen receptor (CAR) specific for disialoganglioside (GD2) that redirected their activity to the immunosuppressive, GD2-expressing neuroblastoma cell line, LAN-1, resisted tumor-induced apoptosis when co-expressing transgenic caAkt. In conclusion, caAkt-transduced T cells showed resistance to several evasion strategies employed by tumors and may therefore enhance the antitumor activity of adoptively transferred T lymphocytes.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Gangliosides,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta,
http://linkedlifedata.com/resource/pubmed/chemical/sialogangliosides
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| pubmed:status |
MEDLINE
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| pubmed:month |
Nov
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| pubmed:issn |
1525-0024
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:volume |
18
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
2006-17
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| pubmed:dateRevised |
2011-11-1
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| pubmed:meshHeading |
pubmed-meshheading:20842106-Apoptosis,
pubmed-meshheading:20842106-Blotting, Western,
pubmed-meshheading:20842106-Cell Proliferation,
pubmed-meshheading:20842106-Flow Cytometry,
pubmed-meshheading:20842106-Gangliosides,
pubmed-meshheading:20842106-Humans,
pubmed-meshheading:20842106-Lymphocyte Activation,
pubmed-meshheading:20842106-NF-kappa B,
pubmed-meshheading:20842106-Neuroblastoma,
pubmed-meshheading:20842106-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:20842106-RNA, Messenger,
pubmed-meshheading:20842106-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:20842106-Signal Transduction,
pubmed-meshheading:20842106-T-Lymphocytes,
pubmed-meshheading:20842106-T-Lymphocytes, Regulatory,
pubmed-meshheading:20842106-Transduction, Genetic,
pubmed-meshheading:20842106-Transforming Growth Factor beta,
pubmed-meshheading:20842106-Tumor Burden,
pubmed-meshheading:20842106-Tumor Cells, Cultured
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| pubmed:year |
2010
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| pubmed:articleTitle |
T cells expressing constitutively active Akt resist multiple tumor-associated inhibitory mechanisms.
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| pubmed:affiliation |
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas 77030, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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