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

Abstract

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 (TR1419) with antitumor efficacy and produced the TR1419 chimeric antigen receptor (CAR) T cells. We characterized the phenotypes and functions of these CAR-T cells and found that the third-generation TR1419-28BBζ CAR-T cells exhibited greater target sensitivity and proliferative capability, with slightly higher PD-1 expression after antigen stimulation. Importantly, we found that the TR1419 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 TR1419 CAR-T cells could serve as a promising strategy for targeting the TRAIL-R1-positive tumors.

• Authors: Yaru Nai, Li Du, Meiying Shen, Tingting Li, Jingjing Huang, Xiaojian Han, Feiyang Luo, Wang Wang, Da Pang, Aishun Jin
• Journal: Frontiers in molecular biosciences (Front Mol Biosci) Vol. 8 Pg. 756599 ( 2021) ISSN: 2296-889X [Print] Switzerland
• PMID: 34988114 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Nai, Du, Shen, Li, Huang, Han, Luo, Wang, Pang and Jin.