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A nanobody-based tri-specific NK cell engager targeting CD5 triggers antitumor immunity

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机构: [1]State Key Laboratory of Biotherapy and Cancer Center, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China [2]Chongqing Institute of Health Resources Innovation, Chongqing 400039, China [3]Department of Hematology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China [4]Blood Research Laboratory, Chengdu Blood Center, Chengdu 610020, China [5]Department of Obstetrics and Gynecology, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China [6]Hematology Department, The General Hospital of Western Theater Command, PLA, Chengdu 610083, China [7]Frontiers Medical Center, Tianfu Jincheng Laboratory, Chengdu 610212, China
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摘要:
The poor prognosis of patients with recurrent or refractory T cell malignancies emphasizes the need for improved immunotherapies. CD5 is a characteristic marker of malignant T cells and is expressed on almost all normal T cells. Therefore, for treating T cell malignancies, focusing on natural killer (NK) cells lacking CD5 expression may elicit a better safety profile than that by T cell-based therapies. We generate a CD5-targeted NK cell engager (NKCE) through the specific binding of CD16a nanobody and a high-affinity anti-CD5 antibody. Its antitumor potency is demonstrated in vitro. After incorporating interleukin (IL)-15Rα/IL-15, the modified tri-NKCE exhibits stronger antitumor efficacy against CD5+ malignant tumor cells, with the production of more cytokines and chemokines. In vivo, tri-NKCE exhibits stronger cytotoxicity by enhancing NK cell proliferation. Compared with chimeric antigen receptor (CAR)-T cells, this tri-NKCE exhibits no toxicity to normal T cells. In conclusion, tri-NKCE offers a safer and cost-effective immunotherapy against T cell malignancies.Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.

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出版当年[2025]版:
大类 | 1 区 医学
小类 | 1 区 医学:研究与实验 2 区 细胞生物学
最新[2025]版:
大类 | 1 区 医学
小类 | 1 区 医学:研究与实验 2 区 细胞生物学
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出版当年[2024]版:
Q1 CELL BIOLOGY Q1 MEDICINE, RESEARCH & EXPERIMENTAL
最新[2024]版:
Q1 CELL BIOLOGY Q1 MEDICINE, RESEARCH & EXPERIMENTAL

影响因子: 最新[2024版] 最新五年平均 出版当年[2024版] 出版当年五年平均 出版前一年[2024版]

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第一作者机构: [1]State Key Laboratory of Biotherapy and Cancer Center, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China [2]Chongqing Institute of Health Resources Innovation, Chongqing 400039, China
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通讯机构: [1]State Key Laboratory of Biotherapy and Cancer Center, Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China [7]Frontiers Medical Center, Tianfu Jincheng Laboratory, Chengdu 610212, China
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