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 cross-linkers 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.
Original language | English (US) |
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Pages (from-to) | 513-517 |
Number of pages | 5 |
Journal | Oncology Reports |
Volume | 18 |
Issue number | 2 |
DOIs | |
State | Published - Aug 2007 |
Externally published | Yes |
Keywords
- Agonistic antibody
- Cross-linker
- Human antigen-binding fragment
- Tumor cells
- Tumor necrosis factor-related apoptosis-inducing ligand receptor