کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1927837 1050262 2016 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Fully human monoclonal antibodies to TRAIL-R1 enhance TRAIL-induced apoptosis via activation of caspase-8 pathway
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Fully human monoclonal antibodies to TRAIL-R1 enhance TRAIL-induced apoptosis via activation of caspase-8 pathway
چکیده انگلیسی
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) or agonistic antibodies targeting TRAIL-receptors (TRAIL-Rs) can selectively induce apoptosis in cancer cells. However, they have limited antitumor efficacy in clinical trials. We previously generated ten fully human monoclonal Abs to TRAIL-receptor type 1 (TR1-mAbs) using immunospot array assay on a chip (ISAAC technology). We found that the TR1-mAbs exhibited different effects on TRAIL-induced apoptosis (enhanced or blocked apoptosis). Here, we further demonstrated that some mAbs competed with TRAIL for binding to TRAIL-R1 expressed on tumor cells that blocked TRAIL-induced apoptosis (B-TR1-Ab), whereas others did not compete with TRAIL that enhanced TRAIL-induced apoptosis (E-TR1-Ab). Combination of E-TR1-Ab (TR1-419) with TRAIL leads to enhanced antitumor activity in various tumor cells in vitro. E-TR1-419 and TRAIL could cooperate to upregulate the mRNA expression and protein levels of TRAIL-R1 and to promote caspase-8 cleavage and increased JNK phosphorylation. Our results suggest that combining E-TR1 Ab with TRAIL could provide a new therapeutic strategy for tumor immunotherapies.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 475, Issue 2, 24 June 2016, Pages 238-244
نویسندگان
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