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The CD39 positive hepatitis B virus surface protein (HBVs)-targeted CAR-T and personalized tumor-reactive CD8+ T cells exhibit potent anti-hepatocellular carcinoma (HCC) activity.

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收录情况： ◇ SCIE

作者：
Zou Fan[1,3,4,5] ; Tan Jizhou[2] ; Liu Ting[2] ; Liu Bingfeng[3,4,5] ; Tang Yaping[1,6,7,8] ; Zhang Hui[3,4,5,*1] ; Li Jiaping[2,*2] ;
机构： [1]Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510623, China [2]Department of Interventional Oncology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510080, China [3]Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, China [4]Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Guangzhou, Guangdong, China [5]Key Laboratory of Tropical Disease Control of Ministry of Education, Guangzhou, Guangdong 510080, China [6]Department of Neurobiology, Southwest Medical University, Luzhou, Sichuan 646000, China [7]Department of Imaging, Affiliated Hospital 3, Zhengzhou University, Zhengzhou 450052, China [8]Guangdong Provincial Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China
出处：
DOI： 10.1016/j.ymthe.2021.01.021
ISSN：

摘要：
CD39, expressed by tumor infiltrating lymphocytes (TILs), is a marker to identify tumor-reactive T cells, which is frequently associated with stronger anti-tumor activity than bystander T cells in a variety of malignancies. Therefore, CD39 could be a promising marker for identifying the active anti-tumor immune cells used for cellular immunotherapy. To test this possibility, we constructed the hepatitis B virus surface protein (HBVs)-specific chimeric antigen receptor T-cells (HBVs-CAR-T cells) and generated the personalized tumor-reactive CD8+ T cells. We subsequently assessed their anti-tumor efficiency mainly with a co-culture system for autologous HBVs-positive HCC organoid and T cells. We found that both CD39+ HBVs-CAR-T and CD39+ personalized tumor-reactive CD8+ T cells induced much more apoptosis in HCC organoids. Although the exhaustion status of CAR-T cells increased in CD39+ CAR-T cells, triple knockdown of PD-1, Tim-3, and Lag-3 with shRNAs furtherly enhanced anti-tumor activity in CD39+ CAR-T cells. Furthermore, these CD39+ CAR-T cells exerted an increased secretion of interferon-γ and stronger anti-tumor effect in patient-derived xenograft mouse model. Our findings demonstrated that CD39 could be a promisingly biomarker to enrich active immune cells and become an indicator marker for evaluating the prognosis of immunotherapy for HCC patients. Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.

基金：
National Natural Science Foundation of China (nos. 81671797, 81971719, and 82003252); the Major Scientific and Technological Project of Guangdong Province (no. 2017B030308006); the Major Program for Tackling Key Problems of Guangzhou City (no. 201704020144); the China Postdoctoral Science Foundation (2019M662853); the Guangdong Key Project in “Development of New Tools for Diagnosis and Treatment of Autism” (2018B030335001); and the Guangzhou Key Project in “Early Diagnosis and Treatment of Autism Spectrum Disorders” (202007030002).
语种：
外文
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中科院(CAS)分区：
出版当年[2021]版：
大类 | 1 区 医学
小类 | 1 区 生物工程与应用微生物 1 区 遗传学 1 区 医学：研究与实验
最新[2023]版：
大类 | 1 区 医学
小类 | 1 区 生物工程与应用微生物 1 区 遗传学 1 区 医学：研究与实验
JCR分区：
出版当年[2021]版：
Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Q1 GENETICS & HEREDITY Q1 MEDICINE, RESEARCH & EXPERIMENTAL
最新[2023]版：
Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Q1 GENETICS & HEREDITY Q1 MEDICINE, RESEARCH & EXPERIMENTAL

影响因子： 最新[2023版] 最新五年平均 出版当年[2021版] 出版当年五年平均 出版前一年[2020版] 出版后一年[2022版]

第一作者：
第一作者机构： [1]Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Hospital, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510623, China [3]Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, China [4]Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Guangzhou, Guangdong, China [5]Key Laboratory of Tropical Disease Control of Ministry of Education, Guangzhou, Guangdong 510080, China
共同第一作者：
通讯作者：
通讯机构： [2]Department of Interventional Oncology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510080, China [3]Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, China [4]Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Guangzhou, Guangdong, China [5]Key Laboratory of Tropical Disease Control of Ministry of Education, Guangzhou, Guangdong 510080, China [*1]Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, China. [*2]Department of Interventional Oncology, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510080, China.
推荐引用方式(GB/T 7714)：
Zou Fan,Tan Jizhou,Liu Ting,et al.The CD39 positive hepatitis B virus surface protein (HBVs)-targeted CAR-T and personalized tumor-reactive CD8+ T cells exhibit potent anti-hepatocellular carcinoma (HCC) activity.[J].MOLECULAR THERAPY.2021,29(5):1794-1807.doi:10.1016/j.ymthe.2021.01.021.
APA：
Zou Fan,Tan Jizhou,Liu Ting,Liu Bingfeng,Tang Yaping...&Li Jiaping.(2021).The CD39 positive hepatitis B virus surface protein (HBVs)-targeted CAR-T and personalized tumor-reactive CD8+ T cells exhibit potent anti-hepatocellular carcinoma (HCC) activity..MOLECULAR THERAPY,29,(5)
MLA：
Zou Fan,et al."The CD39 positive hepatitis B virus surface protein (HBVs)-targeted CAR-T and personalized tumor-reactive CD8+ T cells exhibit potent anti-hepatocellular carcinoma (HCC) activity.".MOLECULAR THERAPY 29..5(2021):1794-1807

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