Source:http://linkedlifedata.com/resource/pubmed/id/17285290
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| Predicate | Object |
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| rdf:type | |
| lifeskim:mentions |
umls-concept:C0018270,
umls-concept:C0027651,
umls-concept:C0039194,
umls-concept:C0085358,
umls-concept:C0087111,
umls-concept:C0178587,
umls-concept:C0332448,
umls-concept:C0442805,
umls-concept:C1332717,
umls-concept:C1413244,
umls-concept:C1416406,
umls-concept:C1706438,
umls-concept:C2348628,
umls-concept:C2698600
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| pubmed:issue |
9
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| pubmed:dateCreated |
2007-6-28
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| pubmed:abstractText |
Interleukin (IL)-21 is a recently discovered cytokine in early clinical development, which has shown anti-tumor activity in various animal models. In the present study, we examine the anti-tumor activity of IL-21 protein therapy in two syngeneic tumor models and its effect on the density of tumor infiltrating T cells. We treated mice bearing established subcutaneous B16 melanomas or RenCa renal cell carcinomas with intraperitoneal (i.p.) or subcutaneous (s.c.) IL-21 protein therapy and subsequently scored the densities of tumor infiltrating CD4(+) and CD8(+) T cells by immunohistochemistry. Whereas both routes of IL-21 administration significantly inhibited growth of small, established RenCa and B16 tumors, only s.c. therapy significantly inhibited the growth of large, established tumors. We found a greater bioavailability and significant drainage of IL-21 to regional lymph nodes following s.c. administration, which could account for the apparent increase in anti-tumor activity. Specific depletion of CD8(+) T cells with monoclonal antibodies completely abrogated the anti-tumor activity, whereas NK1.1(+) cell depletion did not affect tumor growth. In accordance, both routes of IL-21 administration significantly increased the density of tumor infiltrating CD8(+) T cells in both B16 and RenCa tumors; and in the RenCa model s.c. administration of IL-21 led to a significantly higher density of tumor infiltrating CD8(+) T cells compared to i.p. administration. The densities of CD4(+) T cells were unchanged following IL-21 treatments. Taken together, these data demonstrate that IL-21 protein has anti-tumor activity in established syngeneic tumors, and we show that IL-21 therapy markedly increases the density of tumor infiltrating CD8(+) T cells.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Sep
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| pubmed:issn |
0340-7004
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
56
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1417-28
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| pubmed:meshHeading |
pubmed-meshheading:17285290-Animals,
pubmed-meshheading:17285290-Antineoplastic Agents,
pubmed-meshheading:17285290-CD8-Positive T-Lymphocytes,
pubmed-meshheading:17285290-Carcinoma, Renal Cell,
pubmed-meshheading:17285290-Cell Line, Tumor,
pubmed-meshheading:17285290-Female,
pubmed-meshheading:17285290-Infusions, Parenteral,
pubmed-meshheading:17285290-Injections, Subcutaneous,
pubmed-meshheading:17285290-Interleukins,
pubmed-meshheading:17285290-Kidney Neoplasms,
pubmed-meshheading:17285290-Lymphocyte Activation,
pubmed-meshheading:17285290-Lymphocytes, Tumor-Infiltrating,
pubmed-meshheading:17285290-Melanoma, Experimental,
pubmed-meshheading:17285290-Mice,
pubmed-meshheading:17285290-Mice, Inbred BALB C,
pubmed-meshheading:17285290-Mice, Inbred C57BL,
pubmed-meshheading:17285290-T-Lymphocyte Subsets
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| pubmed:year |
2007
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| pubmed:articleTitle |
Interleukin 21 therapy increases the density of tumor infiltrating CD8+ T cells and inhibits the growth of syngeneic tumors.
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| pubmed:affiliation |
Department of Cancer Pharmacology, Biopharmaceuticals Research Unit, Novo Nordisk A/S, Novo Nordisk Park F6.2.30, DK, Måløv, Denmark. hris@novonordisk.com
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| pubmed:publicationType |
Journal Article
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