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T cells expressing CD5/CD7 bispecific chimeric antigen receptors with fully human heavy-chain-only domains mitigate tumor antigen escape

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Signal Transduction and Targeted Therapy 2022年第4期7卷 1322-1333页

作者： Zhenyu Dai Wei Mu Ya Zhao Jiali Cheng Haolong Lin kedong ouyang Xiangyin Jia Jianwei Liu Qiaoe Wei Meng Wang Chaohong Liu Taochao Tan Jianfeng Zhou Department of Hematology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430030China Nanjing IASO Biotherapeutics NanjingJiangsu 210000China Department of Pathogen Biology Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430030China

Bispecific chimeric antigen receptor T-cell(CAR-T)therapies have shown promising results in clinical trials for advanced B-cell ***,it is challenging to broaden the success of bispecific CAR-T therapies to treat refractory/relapse(r/r)T-cell leukemia/lymphoma because targeting multiple T-cell-expressing antigens leads to exacerbated CAR-T cell fratricide and potential safety *** human heavy chain variable(FHVH)antibodies that specifically target CD5 or CD7 were screened and constructed to CD5/CD7 bispecific CARs.A truncated Epidermal growth factor receptor were integrated into CAR constructs to address safety *** tackle the fratricidal issue of CAR-T cells targeting T-cell-pan marker(s),CRISPR/Cas9-based CD5 and CD7 genes knockout were performed before lentiviral transduction of bispecific *** comparison between different bispecific CAR structures:tandem CARs and dual CAR were performed in vitro and in vivo to determine the optimal construct suitable for addressing T-cell malignancy antigen escape in clinical *** of CD5 and CD7 prevents fratricide of CD5/CD7 bispecific CAR-T cells,and FHVH-derived CD5/CD7 bispecific CAR-T cells demonstrate potent antitumor activity in vitro and in *** fratricide-resistant FHVH-derived CD5/CD7 bispecific CAR-T cells have potent antitumor activity against T-cell malignancies,and tandem CARs are more effective than dual CAR in preventing tumor escape in heterogeneous leukemic *** meaningful clinical efficacy and safety of tandem CD5/CD7 CAR-T cells deserve to be explored urgently.

关键词： CD7 CRISPR/Cas9 expressing

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Establishment and characterization of human primary xenograft tumors of pancreatic cancer for pre-clinical phase II like trial for anticancer drug screening and translational research

Establishment and characterization of human primary xenograf...

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2011医学科学前沿论坛第十二届全国肿瘤药理与化疗学术会议

作者： Xiaoran Qin~(1*),ouyang kedong~1,Gang Hu~1,Ying Gu~1,Fubo Xie~1,Ke Wang~1,Zhonghua Tang~1, Dejie Wang,Qiang Zhao,Fu Li~2,Minghua Zhu~3,Zhenzhou Jiang~2,Luyong Zhang~2,Danyi Wen~(1*) 1 Shanghai ChemPartner CO.,LTD.,Building 5,998 Halei Road,Zhangjinag Hi-Tech Park,Shanghai,China 201203 2 China Pharmaceutical University,No.24 Tongjiaxiang,Nanjing,Jiangsu Province,China 210009 3 Changhai Hospital,Shanghai Second Medical University,Shanghai,China 200433.

The risk of pancreatic cancer is increased significantly *** surgery is undertaken primarily in patients with stageⅠand partiallyⅡ*** remains largely ineffective in advanced pancreatic *** develop more effective the... 详细信息

关键词： Pancreatic cancer human primary xengoraft model Gemicitabine

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