Linked Life Data

19920194

Source:http://linkedlifedata.com/resource/pubmed/id/19920194

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
23
pubmed:dateCreated
2009-12-4
pubmed:abstractText
Natural killer (NK) cells are appealing cellular pharmaceuticals for cancer therapy because of their innate ability to recognize and kill tumor cells. Therefore, the development of methods that can enhance the potency in their anticancer effect would be desirable. We have previously shown that a murine granulocyte macrophage colony-stimulating factor (GM-CSF)/interleukin 2 (IL-2) fusion protein displays novel antitumor properties in vivo compared with both cytokines in combination due to recruitment of NK cells. In the present work, we have found that human ortholog of the GM-CSF/IL-2 fusion protein (a.k.a. hGIFT2) induces robust NK cell activation ex vivo with significant secretion of RANTES and a 37-fold increase in IFNgamma production when compared with either IL-2 or GM-CSF single cytokine treatment or their combination. Moreover, hGIFT2 upregulates the expression of NK cell activating receptors NKp44, NKp46, and DNAM-1 (CD226), as well as CD69, CD107a, and IL-2Rbeta expression. In addition, hGIFT2 promotes NK cell maturation, based on the downregulation of CD117 expression and upregulation of CD11b. This phenotype correlates with significantly greater cytotoxicity against tumor cells. At the molecular level, hGIFT2 leads to a potent activation of Janus-activated kinases (JAK) downstream of both IL-2 and GM-CSF receptors (JAK1 and JAK2, respectively) and consequently leads to a hyperphosphorylation of signal transducers and activators of transcription (STAT)1, STAT3, and STAT5. In conclusion, hGIFT2 fusokine possesses unique biochemical properties distinct from IL-2 and GM-CSF, constitutes a novel and potent tool for ex vivo NK cell activation and maturation, and may be of use for cancer cell immunotherapy.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1538-7445
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
69
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
9020-8
pubmed:dateRevised
2010-7-21
pubmed:meshHeading
pubmed-meshheading:19920194-Amino Acid Sequence, pubmed-meshheading:19920194-Cell Line, pubmed-meshheading:19920194-DNA, Complementary, pubmed-meshheading:19920194-Granulocyte-Macrophage Colony-Stimulating Factor, pubmed-meshheading:19920194-Humans, pubmed-meshheading:19920194-Interleukin-2, pubmed-meshheading:19920194-Janus Kinases, pubmed-meshheading:19920194-Killer Cells, Natural, pubmed-meshheading:19920194-Leukocytes, Mononuclear, pubmed-meshheading:19920194-Lymphocyte Activation, pubmed-meshheading:19920194-Molecular Sequence Data, pubmed-meshheading:19920194-Receptors, Immunologic, pubmed-meshheading:19920194-Recombinant Fusion Proteins, pubmed-meshheading:19920194-STAT Transcription Factors, pubmed-meshheading:19920194-Signal Transduction, pubmed-meshheading:19920194-Up-Regulation
pubmed:year
2009
pubmed:articleTitle
The human ortholog of granulocyte macrophage colony-stimulating factor and interleukin-2 fusion protein induces potent ex vivo natural killer cell activation and maturation.
pubmed:affiliation
Department of Medicine, Division of Experimental Medicine, McGill University, Canada.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't