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TRAIL-R1-targeted chimeric antigen receptor T cells exhibit dual antitumor effects
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  • AiShun Jin,
  • Yaru Nai,
  • Li Du,
  • Meiying Shen,
  • Tingting Li,
  • Jingjing Huang,
  • xiaojian Han,
  • Feiyang Luo,
  • Da Pang
AiShun Jin
Chongqing Medical University
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Yaru Nai
Chongqing Medical University
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Li Du
Chongqing Medical University
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Meiying Shen
Harbin Medical University Cancer Hospital
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Tingting Li
Chongqing Medical University
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Jingjing Huang
Chongqing Medical University
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xiaojian Han
Chongqing Medical University
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Feiyang Luo
Chongqing Medical University
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Da Pang
Harbin Medical University Cancer Hospital
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Abstract

Tumor necrosis factor-related apoptosis-inducing ligand receptor 1 (TRAIL-R1) has limited expression in normal tissues but highly expression in a broad range of tumors, making it an attractive target for cancer immunotherapy. We have previously prepared a fully human monoclonal antibody targeting TRAIL-R1 (TR1419), which can specifically induce apoptosis in antigen-positive tumor cells. Here, we prepared the TR1419CAR-T cells using the single chain variable fragment (scFv) from TR1419, which were evaluated for the phenotypes and function. The TR1419CAR-T cells induced cytolysis of TRAIL-R1-positive tumor cells not only via activation of the death receptor-dependent apoptotic pathway, but also via T-cell mediated cytotoxicity. Furthermore, compared to the second-generation TR1419-28ζ and TR1419-BBζ CAR-T cells, the third-generation TR1419-28BBζ CAR-T cells had greater sensitivity to target antigen, exhibited a better proliferative ability, but showed slightly higher PD-1 expression after antigen stimulation. Altogether, TR1419CAR-T cells, especially TR1419-28BBζCAR-T cells could be a promising treatment strategy for TRAIL-R1 positive tumors.

Peer review status:IN REVISION

10 May 2021Submitted to Clinical & Experimental Immunology
11 May 2021Assigned to Editor
11 May 2021Submission Checks Completed
24 May 2021Reviewer(s) Assigned
13 Jun 2021Review(s) Completed, Editorial Evaluation Pending
13 Jun 2021Editorial Decision: Revise Major