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Programming CAR T cells to enhance anti-tumor efficacy through remodeling of the immune system
Xiaohui Wang, Zhiqiang Wu, Wei Qiu, Ping Chen, Xiang Xu, Weidong Han
《医学前沿(英文)》 2020年 第14卷 第6期 页码 726-745 doi: 10.1007/s11684-020-0746-0
关键词: CAR T cells immunoregulatory molecules endogenous immune response solid malignancies
CAR T-cell immunotherapy: a powerful weapon for fighting hematological B-cell malignancies
《医学前沿(英文)》 2021年 第15卷 第6期 页码 783-804 doi: 10.1007/s11684-021-0904-z
CAR T cells redirected against tumor-specific antigen glycoforms: can low-sugar antigens guarantee a
《医学前沿(英文)》 2022年 第16卷 第3期 页码 322-338 doi: 10.1007/s11684-021-0901-2
关键词: cancer immunotherapy chimeric antigen receptor solid tumors tumor-associated antigen glycosylation O-glycans adoptive cell therapy
《医学前沿(英文)》 doi: 10.1007/s11684-023-1010-1
关键词: exosomes induce activation impair function CD19 exosomal CD19 antigen
嵌合抗原受体和调节性T细胞——移植中人类白细胞抗原特异性免疫抑制的潜力 Review
Sabrina Wright, Conor Hennessy, Joanna Hester, Fadi Issa
《工程(英文)》 2022年 第10卷 第3期 页码 30-43 doi: 10.1016/j.eng.2021.10.018
嵌合抗原受体(CAR)是基因工程领域的一项突破,它彻底改变了过继细胞疗法(ACT)领域。表达这些受体的细胞通过在合成的CAR构建体中包含抗原特异性结合区域而被重新定向到预定的靶点。与常规T细胞(Tconvs)不同,调节性T细胞(Treg)在抑制免疫激活和调节宿主免疫反应方面发挥着重要作用。然而,目前对CAR-Treg 工程的研究非常有限,并且关于治疗用途的最佳设计存在不确定性。本文综述了CAR-Treg 发展的理论基础、其对人类移植的意义、潜在的设计、安全性考虑因素,以及迄今为止CAR-Treg在移植模型中的对比。
关键词: 嵌合抗原受体(CAR) 调节性T细胞 异性免疫 CAR设计 基因编辑
CAR-T细胞产品的质量控制和非临床研究——一般原则和关键问题 Review
李永红, 霍艳, 于雷, 王军志
《工程(英文)》 2019年 第5卷 第1期 页码 122-131 doi: 10.1016/j.eng.2018.12.003
采用嵌合抗原受体T 细胞(chimeric antigen receptor T cells, CAR-T cells)的过继性细胞治疗是一种很有前途的肿瘤免疫治疗策略,近年来发展迅速。CAR-T 细胞是通过基因修饰能够特异性识别肿瘤细胞表面特定抗原的T 细胞,对肿瘤细胞具有强大的杀灭作用。目前CAR-T 细胞在恶性血液病患者中的临床应用已经取得振奋人心的结果,国内外对于CAR-T 细胞针对多种靶点以及用于治疗实体瘤的研究开发形成了很大的热点,越来越多的产品将会进入临床试验和上市使用。本文在相关细胞治疗和基因治疗产品指导原则的基础上,结合CAR-T 细胞产品的具体特点,探讨其质量控制和非临床前研究的一般原则,以及其中的一些关键问题。
CRISPR-Cas9 mediated LAG-3 disruption in CAR-T cells
null
《医学前沿(英文)》 2017年 第11卷 第4期 页码 554-562 doi: 10.1007/s11684-017-0543-6
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 T cell activity is lymphocyte activation gene-3 (LAG-3). We successfully generated LAG-3 knockout T and 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.
关键词: CAR-T CRISPR-Cas9 LAG-3
Innate and adaptive T cells in influenza disease
null
《医学前沿(英文)》 2018年 第12卷 第1期 页码 34-47 doi: 10.1007/s11684-017-0606-8
Influenza is a major global health problem, causing infections of the respiratory tract, often leading to acute pneumonia, life-threatening complications and even deaths. Over the last seven decades, vaccination strategies have been utilized to protect people from complications of influenza, especially groups at high risk of severe disease. While current vaccination regimens elicit strain-specific antibody responses, they fail to generate cross-protection against seasonal, pandemic and avian viruses. Moreover, vaccines designed to generate influenza-specific T-cell responses are yet to be optimized. During natural infection, viral replication is initially controlled by innate immunity before adaptive immune responses (T cells and antibody-producing B cells) achieve viral clearance and host recovery. Adaptive T and B cells maintain immunological memory and provide protection against subsequent infections with related influenza viruses. Recent studies also shed light on the role of innate T-cells (MAIT cells, gd T cells, and NKT cells) in controlling influenza and linking innate and adaptive immune mechanisms, thus making them attractive targets for vaccination strategies. We summarize the current knowledge on influenza-specific innate MAIT and gd T cells as well as adaptive CD8+ and CD4+ T cells, and discuss how these responses can be harnessed by novel vaccine strategies to elicit cross-protective immunity against different influenza strains and subtypes.
关键词: influenza innate T cells CD4+ and CD8+ T cells vaccination
null
《医学前沿(英文)》 2018年 第12卷 第3期 页码 262-268 doi: 10.1007/s11684-017-0584-x
γδ T cells display unique developmental, distributional, and functional patterns and can rapidly respond to various insults and contribute to diverse diseases. Different subtypes of γδ T cells are produced in the thymus prior to their migration to peripheral tissues. γδ T cells are enriched in the liver and exhibit liver-specific features. Accumulating evidence reveals that γδ T cells play important roles in liver infection, non-alcoholic fatty liver disease, autoimmune hepatitis, liver fibrosis and cirrhosis, and liver cancer and regeneration. In this study, we review the properties of hepatic γδ T cells and summarize the roles of γδ T cells in liver diseases. We believe that determining the properties and functions of γδ T cells in liver diseases enhances our understanding of the pathogenesis of liver diseases and is useful for the design of novel γδ T cell-based therapeutic regimens for liver diseases.
关键词: γδT cells liver infection non-alcoholic fatty liver disease autoimmune hepatitis liver fibrosis and cirrhosis liver cancer liver regeneration
Chimeric antigen receptor T cell therapies for acute myeloid leukemia
Bin Gu, Jianhong Chu, Depei Wu
《医学前沿(英文)》 2020年 第14卷 第6期 页码 701-710 doi: 10.1007/s11684-020-0763-z
High-affinity T cell receptors redirect cytokine-activated T cells (CAT) to kill cancer cells
Synat Kang, Yanyan Li, Yifeng Bao, Yi Li
《医学前沿(英文)》 2019年 第13卷 第1期 页码 69-82 doi: 10.1007/s11684-018-0677-1
Cytokine-activated T cells (CATs) can be easily expanded and are widely applied to cancer immunotherapy. However, the good efficacy of CATs is rarely reported in clinical applications because CATs have no or very low antigen specificity. The low-efficacy problem can be resolved using T cell antigen receptor-engineered CAT (TCR-CAT). Herein, we demonstrate that NY-ESO-1157–165 HLA-A*02:01-specific high-affinity TCR (HAT)-transduced CATs can specifically kill cancer cells with good efficacy. With low micromolar range dissociation equilibrium constants, HAT-transduced CATs showed good specificity with no off-target killing. Furthermore, the high-affinity TCR-CATs delivered significantly better activation and cytotoxicity than the equivalent TCR-engineered T cells (TCR-Ts) in terms of interferon-g and granzyme B production and in vitro cancer cell killing ability. TCR-CAT may be a very good alternative to the expensive TCR-T, which is considered an effective personalized cyto-immunotherapy.
关键词: cytokine-activated T cells high-affinity T cell receptor cancer immunotherapy TCR-CAT
调节性T细胞及其在抗肿瘤免疫疗法中的临床应用 Review
解丰, 梁瑞, 李丹, 李斌
《工程(英文)》 2019年 第5卷 第1期 页码 132-139 doi: 10.1016/j.eng.2018.12.002
《医学前沿(英文)》 2022年 第16卷 第2期 页码 285-294 doi: 10.1007/s11684-021-0843-8
关键词: CAR-T cell therapy refractory diffuse large B-cell lymphoma cytokine release syndrome dose-limiting toxicity
从药物开发的角度看工程化T细胞疗法 Review
Fang Chen, Joseph A. Fraietta, Carl H. June, 许中伟, J. Joseph Melenhorst, Simon F. Lacey
《工程(英文)》 2019年 第5卷 第1期 页码 140-149 doi: 10.1016/j.eng.2018.11.010
Management of cytokine release syndrome related to CAR-T cell therapy
Hongli Chen, Fangxia Wang, Pengyu Zhang, Yilin Zhang, Yinxia Chen, Xiaohu Fan, Xingmei Cao, Jie Liu, Yun Yang, Baiyan Wang, Bo Lei, Liufang Gu, Ju Bai, Lili Wei, Ruili Zhang, Qiuchuan Zhuang, Wanggang Zhang, Wanhong Zhao, Aili He
《医学前沿(英文)》 2019年 第13卷 第5期 页码 610-617 doi: 10.1007/s11684-019-0714-8
关键词: chimeric antigen receptor T cell cytokine release syndrome tocilizumab
标题 作者 时间 类型 操作
Programming CAR T cells to enhance anti-tumor efficacy through remodeling of the immune system
Xiaohui Wang, Zhiqiang Wu, Wei Qiu, Ping Chen, Xiang Xu, Weidong Han
期刊论文
CAR T cells redirected against tumor-specific antigen glycoforms: can low-sugar antigens guarantee a
期刊论文
exosomes induce initial activation by exosomal CD19 antigen but impair the function of CD19-specific CART-cells via TGF-β signaling
期刊论文
Chimeric antigen receptor T cell therapies for acute myeloid leukemia
Bin Gu, Jianhong Chu, Depei Wu
期刊论文
High-affinity T cell receptors redirect cytokine-activated T cells (CAT) to kill cancer cells
Synat Kang, Yanyan Li, Yifeng Bao, Yi Li
期刊论文
Phase I study of CBM.CD19 chimeric antigen receptor T cell in the treatment of refractory diffuse large
期刊论文
从药物开发的角度看工程化T细胞疗法
Fang Chen, Joseph A. Fraietta, Carl H. June, 许中伟, J. Joseph Melenhorst, Simon F. Lacey
期刊论文
Management of cytokine release syndrome related to CAR-T cell therapy
Hongli Chen, Fangxia Wang, Pengyu Zhang, Yilin Zhang, Yinxia Chen, Xiaohu Fan, Xingmei Cao, Jie Liu, Yun Yang, Baiyan Wang, Bo Lei, Liufang Gu, Ju Bai, Lili Wei, Ruili Zhang, Qiuchuan Zhuang, Wanggang Zhang, Wanhong Zhao, Aili He
期刊论文