Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2004-2-20
pubmed:abstractText
Adult T-cell leukemia/lymphoma (ATL) is an aggressive lymphoid proliferative disease that exists under diverse clinical forms ranging from chronic to acute. Although leukemic cells from patients with ATL exhibit an intrinsic resistance to chemotherapy, monoclonal antibodies directed against CD25 (interleukin 2 receptor alpha [IL-2Ralpha] antibody) have been used as specific therapeutic agents. However, significant clinical results with these antibodies have been demonstrated only in chronic forms of ATL. In contrast to resting T cells, human T-cell lymphotropic virus type 1 (HTLV-1)-infected cells constitutively express high levels of surface transferrin receptor (TfR). Herein, we report the characterization of a new monoclonal antibody (mAb A24) directed against the human TfR and the evaluation of its capacity to block the proliferation of ATL cells ex vivo. We determined that A24 binds TfR with an equilibrium constant (K'd) of 2.7 nM and competes with transferrin for binding to TfR. A24 also inhibited [55Fe]-transferrin uptake in activated T cells and blocked T-cell proliferation. Moreover, A24 reduced and impaired TfR expression and recycling, respectively. Most important, we showed that A24 blocked the ex vivo proliferation of malignant T cells from both acute and chronic forms of ATL, through induction of programmed cell death. Therefore efficient therapeutic tools to treat acute forms of ATL might be derived from A24.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
103
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1838-45
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:14592824-Antibodies, Monoclonal, pubmed-meshheading:14592824-Apoptosis, pubmed-meshheading:14592824-Cell Death, pubmed-meshheading:14592824-Cell Division, pubmed-meshheading:14592824-Dose-Response Relationship, Drug, pubmed-meshheading:14592824-Flow Cytometry, pubmed-meshheading:14592824-Human T-lymphotropic virus 1, pubmed-meshheading:14592824-Humans, pubmed-meshheading:14592824-Iron, pubmed-meshheading:14592824-Kinetics, pubmed-meshheading:14592824-Leukemia, T-Cell, pubmed-meshheading:14592824-Leukocytes, Mononuclear, pubmed-meshheading:14592824-Lymphocyte Activation, pubmed-meshheading:14592824-Microscopy, Confocal, pubmed-meshheading:14592824-Protein Binding, pubmed-meshheading:14592824-Receptors, Interleukin-2, pubmed-meshheading:14592824-Receptors, Transferrin, pubmed-meshheading:14592824-Surface Plasmon Resonance, pubmed-meshheading:14592824-T-Lymphocytes, pubmed-meshheading:14592824-Transferrin
pubmed:year
2004
pubmed:articleTitle
A neutralizing monoclonal antibody (mAb A24) directed against the transferrin receptor induces apoptosis of tumor T lymphocytes from ATL patients.
pubmed:affiliation
Institut National de la Santé et de la Recherche Médicale (INSERM) E-0225, Faculté de Médecine Xavier Bichat, Paris, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't