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• W2068711271 abstract "TRA-8 is an agonistic mouse monoclonal antibody that binds to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptor 5, which induces apoptosis in cancer cells through a caspase-8-dependent mechanism. We investigated the ability of TRA-8 to augment the radiotherapy (RT) and chemotherapy response of human glioma cells in vitro and in vivo.The in vitro cytotoxicity of TRA-8 and temozolomide (Tmz) or RT was examined using adenosine triphosphate-dependent viability and clonogenic survival assays with five glioma cell lines. Death receptor 5 expression was determined by flow cytometry. In vivo studies included subcutaneous and intracranial xenograft models testing various combination treatments, including RT, Tmz, and TRA-8.TRA-8, combined with Tmz or RT, produced enhanced cytotoxicity against five glioma cell lines compared with the use of the individual agents alone. Death receptor 5 upregulation occurred in response to RT. Complete tumor regression in the subcutaneous experiments was the most common in animals that received combination therapy with TRA-8/Tmz/RT. TRA-8 enhanced tumor growth delay in combination with RT or Tmz. TRA-8 alone had limited activity against intracranial tumors. In contrast, the median survival of mice treated with TRA-8/Tmz/RT was significantly greater than the control or TRA-8-alone-treated mice. The median survival of the mice treated with TRA-8/Tmz/RT or chemoradiotherapy only was significantly greater than the control or TRA-8-treated mice. A trend toward improved survival was observed between TRA-8/Tmz/RT-treated and Tmz/RT-treated mice.These preliminary findings support the hypothesis that TRA-8 will augment the RT and chemotherapy response in gliomas. A humanized version of TRA-8 is being evaluated in a Phase II clinical trial." @default.
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• W2068711271 date "2008-06-01" @default.
• W2068711271 modified "2023-09-23" @default.
• W2068711271 title "Enhancement of Glioma Radiotherapy and Chemotherapy Response With Targeted Antibody Therapy Against Death Receptor 5" @default.
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• W2068711271 doi "https://doi.org/10.1016/j.ijrobp.2008.02.005" @default.
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