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Effect of a novel fully human monovalent antigen-binding fragment on the survival of cancer cell lines.

Authors
Kwon, YS; Lee, YR; Kim, YS; Lee, HW; Jang, YJ
Citation
Oncology reports, 18(2):513-517, 2007
Journal Title
Oncology reports
ISSN
1021-335X1791-2431
Abstract
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytokine having potent cytotoxic activity specifically to tumor cells. Agonistic antibodies against TRAIL receptors are currently being explored as anti-cancer therapeutics. Here, we report studies on JKTR-18, a monovalent human monoclonal antibody Fab selected against human recombinant TRAIL receptor 2 (DR5) by phage display technology. It induced cell death in Jurkat and HL60 leukemia cell lines without the need for secondary crosslinkers in vitro. It did not compete with soluble TRAIL (sTRAIL) for binding to DR5, and its combination with sTRAIL resulted in greater cell death than either agent alone. The cell death induced by JKTR-18 included a caspase-independent mechanism. This is the first report of a monovalent antibody fragment against TRAIL receptor that can induce tumor cell death in the absence of a crosslinker.
MeSH terms
Amino Acid Chloromethyl Ketones/pharmacologyAmino Acid SequenceAntibodies, Monoclonal/geneticsAntibodies, Monoclonal/immunologyAntibodies, Monoclonal/pharmacology*Apoptosis/drug effectsCaspase 3/antagonists & inhibitorsCaspase 3/metabolismCaspase 7/antagonists & inhibitorsCaspase 7/metabolismCell Survival/drug effectsCysteine Proteinase Inhibitors/pharmacologyDNA Fragmentation/drug effectsDose-Response Relationship, DrugEnzyme-Linked Immunosorbent AssayFlow CytometryHL-60 CellsHumansImmunoglobulin Fab Fragments/geneticsImmunoglobulin Fab Fragments/immunologyImmunoglobulin Fab Fragments/pharmacology*Jurkat CellsLeukemia/metabolismLeukemia/pathologyMolecular Sequence DataProtein Binding/immunologyReceptors, TNF-Related Apoptosis-Inducing Ligand/immunology*Receptors, TNF-Related Apoptosis-Inducing Ligand/pharmacologyTime Factors
PMID
17611678
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Microbiology
AJOU Authors
장, 영주
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