抄録
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.
本文言語 | 英語 |
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ページ(範囲) | 238-244 |
ページ数 | 7 |
ジャーナル | Biochemical and Biophysical Research Communications |
巻 | 475 |
号 | 2 |
DOI | |
出版ステータス | 出版済み - 2016/06/24 |
ASJC Scopus 主題領域
- 生物理学
- 生化学
- 分子生物学
- 細胞生物学