Linked Life Data

18369620

Source:http://linkedlifedata.com/resource/pubmed/id/18369620

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2008-9-23
pubmed:abstractText
We have previously reported that a single-chain T cell receptor/IL-2 fusion protein (scTCR-IL2) exhibits potent targeted antitumor activity in nude mice bearing human tumor xenografts that display cognate peptide/HLA complexes. In this study, we further explore the mechanism of action of this molecule. We compared the biological activities of c264scTCR-IL2, a scTCR-IL2 protein recognizing the aa264-272 peptide of human p53, with that of MART-1scTCR-IL2, which recognizes the MART-1 melanoma antigen (aa27-35). In vitro studies showed that c264scTCR-IL2 and MART-1scTCR-IL2 were equivalent in their ability to bind cell-surface IL-2 receptors and stimulate NK cell responses. In mice, MART-1scTCR-IL2 was found to have a twofold longer serum half-life than c264scTCR-IL2. However, despite its shorter serum half-life, c264scTCR-IL2 showed significantly better antitumor activity than MART-1scTCR-IL2 against p53(+)/HLA-A2(+) tumor xenografts. The more potent antitumor activity of c264scTCR-IL2 correlated with an enhanced capacity to promote NK cell infiltration into tumors. Similar differences in antigen-dependent tumor infiltration were observed with activated splenocytes pre-treated in vitro with c264scTCR-IL2 or MART-1scTCR-IL2 and then transferred into p53(+)/HLA-A2(+) tumor bearing recipients. The data support a model where c264scTCR-IL2 activates immune cells to express IL-2 receptors. Following stable interactions with cell-surface IL-2 receptors, c264scTCR-IL2 fusion molecule enhances the trafficking of immune cells to tumors displaying target peptide/HLA complexes where the immune cells mediate antitumor effects. Thus, this type of fusion molecule could be used directly as a targeted immunotherapeutic or in adoptive cell transfer approaches to activate and improve the anti-cancer activities of immune cells by providing them with pre-selected antigen recognition capability.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0340-7004
pubmed:author
pubmed:issnType
Print
pubmed:volume
57
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1781-94
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:18369620-Animals, pubmed-meshheading:18369620-Antigens, Neoplasm, pubmed-meshheading:18369620-Female, pubmed-meshheading:18369620-Flow Cytometry, pubmed-meshheading:18369620-Half-Life, pubmed-meshheading:18369620-Humans, pubmed-meshheading:18369620-Immunohistochemistry, pubmed-meshheading:18369620-Immunotherapy, pubmed-meshheading:18369620-Interleukin-2, pubmed-meshheading:18369620-Killer Cells, Natural, pubmed-meshheading:18369620-Lymphocyte Activation, pubmed-meshheading:18369620-MART-1 Antigen, pubmed-meshheading:18369620-Melanoma, Experimental, pubmed-meshheading:18369620-Mice, pubmed-meshheading:18369620-Mice, Nude, pubmed-meshheading:18369620-Neoplasm Proteins, pubmed-meshheading:18369620-Receptors, Antigen, T-Cell, pubmed-meshheading:18369620-Recombinant Fusion Proteins, pubmed-meshheading:18369620-Tumor Suppressor Protein p53, pubmed-meshheading:18369620-Xenograft Model Antitumor Assays
pubmed:year
2008
pubmed:articleTitle
Targeting activity of a TCR/IL-2 fusion protein against established tumors.
pubmed:affiliation
Altor Bioscience Corporation, 2810 N Commerce Parkway, Miramar, FL, 33025, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural