Linked Life Data

15569983

Source:http://linkedlifedata.com/resource/pubmed/id/15569983

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
22
pubmed:dateCreated
2004-11-30
pubmed:abstractText
Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell neoplasm with dismal prognosis, and no optimal therapy has been developed. We tested the defucosylated chimeric anti-CC chemokine receptor 4 (CCR4) monoclonal antibody, KM2760, to develop a novel immunotherapy for this refractory tumor. In the presence of peripheral blood mononuclear cells (PBMCs) from healthy adult donors, KM2760 induced CCR4-specific antibody-dependent cellular cytotoxicity (ADCC) against CCR4-positive ATLL cell lines and primary tumor cells obtained from ATLL patients. We next examined the KM2760-induced ADCC against primary ATLL cells in an autologous setting. Antibody-dependent cellular cytotoxicity mediated by autologous effector cells was generally lower than that mediated by allogeneic control effector cells. However, a robust ADCC activity was induced in some cases, which was comparable with that mediated by allogeneic effector cells. It suggests that the ATLL patients' PBMCs retain substantial ADCC-effector function, although the optimal conditions for maximal effect have not yet been determined. In addition, we also found a high expression of FoxP3 mRNA and protein, a hallmark of regulatory T cells, in ATLL cells, indicating the possibility that ATLL cells originated from regulatory T cells. KM2760 reduced FoxP3 mRNA expression in normal PBMCs along with CCR4 mRNA by lysis of CCR4+ T cells in vitro. Our data suggest not only that the CCR4 molecule could be a suitable target for the novel antibody-based therapy for patients with ATLL but also that KM2760 may induce effective tumor immunity by reducing the number of regulatory T cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1078-0432
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7529-39
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:15569983-Antibodies, Monoclonal, pubmed-meshheading:15569983-Antigens, CD3, pubmed-meshheading:15569983-Blotting, Western, pubmed-meshheading:15569983-Cell Line, Tumor, pubmed-meshheading:15569983-Cell Proliferation, pubmed-meshheading:15569983-DNA-Binding Proteins, pubmed-meshheading:15569983-Dose-Response Relationship, Drug, pubmed-meshheading:15569983-Flow Cytometry, pubmed-meshheading:15569983-Forkhead Transcription Factors, pubmed-meshheading:15569983-Genotype, pubmed-meshheading:15569983-Humans, pubmed-meshheading:15569983-Immunotherapy, pubmed-meshheading:15569983-Leukemia-Lymphoma, Adult T-Cell, pubmed-meshheading:15569983-Leukocytes, Mononuclear, pubmed-meshheading:15569983-RNA, Messenger, pubmed-meshheading:15569983-Receptors, CCR4, pubmed-meshheading:15569983-Receptors, Chemokine, pubmed-meshheading:15569983-Receptors, IgG, pubmed-meshheading:15569983-Reverse Transcriptase Polymerase Chain Reaction
pubmed:year
2004
pubmed:articleTitle
The CC chemokine receptor 4 as a novel specific molecular target for immunotherapy in adult T-Cell leukemia/lymphoma.
pubmed:affiliation
Department of Internal Medicine & Molecular Science, Nagoya City University Graduate School of Medical Sciences, Aichi, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't