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CRISPR-Cas9 mediated LAG-3 disruption in CAR-T cells

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收录情况： ◇ SCIE ◇ 统计源期刊 ◇ CSCD-C

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机构： [1]Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China [2]State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing100190, China [3]University of Chinese Academy of Sciences, Beijing 100049, China [4]Graduate School, University of Science and Technology of China, Hefei 230026, China [5]Department of Pathology, Immunology and Laboratory Medicine, University of Florida, FL 32611, USA [6]Beijing Cord Blood Bank, Beijing100176, China

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关键词： CAR-T CRISPR-Cas9 LAG-3

摘要：

T cells engineered with chimeric antigen receptor (CAR) have been successfully applied to treat advanced refractory B cell malignancy. However, many challenges remain in extending its application toward the treatment of solid tumors. The immunosuppressive nature of tumor microenvironment is considered one of the key factors limiting CAR-T efficacy. One negative regulator of Tcell activity is lymphocyte activation gene-3 (LAG-3). We successfully generated LAG-3 knockout Tand CAR-T cells with high efficiency using CRISPR-Cas9 mediated gene editing and found that the viability and immune phenotype were not dramatically changed during in vitro culture. LAG-3 knockout CAR-T cells displayed robust antigen-specific antitumor activity in cell culture and in murine xenograft model, which is comparable to standard CAR-T cells. Our study demonstrates an efficient approach to silence immune checkpoint in CAR-T cells via gene editing.

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出版当年[2016]版：

大类 | 4 区医学

小类 | 4 区医学：研究与实验 4 区肿瘤学

最新[2023]版：

大类 | 3 区医学

小类 | 3 区医学：研究与实验 4 区肿瘤学

JCR分区：

出版当年[2015]版：

Q3 MEDICINE, RESEARCH & EXPERIMENTAL Q4 ONCOLOGY

最新[2023]版：

Q2 MEDICINE, RESEARCH & EXPERIMENTAL Q2 ONCOLOGY

影响因子： 3.9 最新[2023版] 5.4 最新五年平均 1.863 出版当年[2015版] 0 出版当年五年平均 0 出版前一年[2014版] 1.634 出版后一年[2016版]

第一作者：

第一作者机构： [1]Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China

通讯作者：

通讯机构： [1]Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China [2]State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing100190, China [3]University of Chinese Academy of Sciences, Beijing 100049, China [5]Department of Pathology, Immunology and Laboratory Medicine, University of Florida, FL 32611, USA

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