TRAIL-R1-Targeted CAR-T Cells Exhibit Dual Antitumor Efficacy

作者：Yaru Nai, Li Du, Meiying Shen, Tingting Li, Jingjing Huang, Xiaojian Han, Feiyang Luo, Wang Wang, Da Pang, Aishun Jin · 发表于：Frontiers in Molecular Biosciences · 年份：2021 · DOI：10.3389/fmolb.2021.756599 · 被引用次数：13 · 研究领域：CAR-T cell therapy research、Virus-based gene therapy research、Nanowire Synthesis and Applications

Tumor necrosis factor–related apoptosis-inducing ligand receptor 1 (TRAIL-R1) has limited expression in normal tissues but was highly expressed in various types of tumors, making it an attractive target for cancer immunotherapy. Here, we utilized the single-chain variable fragment (scFv) from our previously identified TRAIL-R1–targeting monoclonal antibody (TR1 419 ) with antitumor efficacy and produced the TR1 419 chimeric antigen receptor (CAR) T cells. We characterized the phenotypes and functions of these CAR-T cells and found that the third-generation TR1 419 -28BBζ CAR-T cells exhibited greater target sensitivity and proliferative capability, with slightly higher PD-1 expression after antigen stimulation. Importantly, we found that the TR1 419 CAR-T cells could induce TRAIL-R1–positive tumor cell death via a dual mechanism of the death receptor–dependent apoptosis as well as the T-cell–mediated cytotoxicity. Altogether, the TR1 419 CAR-T cells could serve as a promising strategy for targeting the TRAIL-R1–positive tumors.