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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

摘要:

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。Treg 中CAR的表达被认为是治疗自身免疫和炎症性疾病、移植物抗宿主病(GVHD)和器官移植排斥反应的一种方法。在后者中,它们作为同种异体移植受者免疫耐受的介质具有巨大的潜力。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

摘要:

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。

关键词: 嵌合抗原受体T细胞     质量控制     非临床研究     安全性     有效性     临床试验     癌症免疫治疗    

基于自然杀伤细胞的癌症免疫疗法的进展和前景 Review

胡渊, 田志刚, 张彩

《工程(英文)》 2019年 第5卷 第1期   页码 106-114 doi: 10.1016/j.eng.2018.11.015

摘要: 这些策略包括:上调自然杀伤细胞抑制性受体的配体,产生可溶性分子或免疫抑制因子。近来,嵌合抗原受体(chimeric antigen receptor,CAR)修饰的自然杀伤细胞因其再导向特异性和有效的抗肿瘤活性而展现出巨大潜力。

关键词: 自然杀伤细胞     免疫疗法     癌症     临床试验     嵌合抗原受体    

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

摘要: 例如,经基因修饰后,T 细胞可表达嵌合抗原受体(chimeric antigen receptor,CAR),使其能够识别并杀死肿瘤细胞,并形成一个记忆库,准备回击持续存在的恶性细胞。抗CD19 嵌合抗原受体T 细胞(CAR T cells,CART19)对某些恶性肿瘤具有显著的临床疗效。本文综述了基于生物标志物的分析方法在优化CAR结构、临床前研究和临床疗效评价、不良反应(AE)和CART19 细胞动力学方面的应用。同时还探讨了能够发现最佳靶标、新型CAR 结合结构域以及预测临床反应和不良反应的生物标志物的先进技术和计算工具。

关键词: 工程化T细胞疗法     嵌合抗原受体     药物开发过程     生物标志物     CAR19     CART19    

中国私用轿车发展的现状与问题

郭孔辉

《中国工程科学》 2000年 第2卷 第8期   页码 25-30

摘要:

目前国内对中国应不应该发展私用轿车,中国应着重发展什么样的轿车,中国应不应该发展自己的轿车工业,中国轿车工业的出路在哪里,以及应如何发展中国的轿车工业,……等等,讨论颇多,已经成为社会上普遍关心的问题。文章试图分析目前提出的有代表性的各种观点,并对有关问题提出笔者自己的见解,以供参考。笔者认为解决"汽车灾难"问题的根本出路不在抑制私用轿车的发展,而在于发展汽车高新技术,加强城市规划与交通管理。文章在肯定引进合资对提高我国汽车制造技术和管理水平的重要作用的同时,指出它的负面影响是逐渐丧失产品开发的主动权;提出中国汽车工业的总战略应是:"自强不息加国际合作",其中包括:高新技术战略、自主双赢战略、内联自强战略、自主品牌战略和跨越赶超战略。

关键词: 中国汽车工业     私用轿车     家用轿车     现状与问题    

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

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 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    

Thermal response of steel framing members in open car park fires

Xia YAN; Marion CHARLIER; Thomas GERNAY

《结构与土木工程前沿(英文)》 2022年 第16卷 第9期   页码 1071-1088 doi: 10.1007/s11709-022-0879-0

摘要: For open car park structures, adopting a performance-based structural fire design is often justified and allowed because the fire does not reach flashover. However, this design approach requires an accurate assessment of temperatures in structural members exposed to car fires. This paper describes a numerical study on the thermal exposure on steel framing members in open car park fires. Steel temperatures are computed by the coupling of computational fluid dynamics and finite element modeling, and by analytical models from the Eurocodes. In addition, the influence of galvanization on the steel temperature evolution is assessed. Results show that temperatures in unprotected beams and columns are influenced by the section geometry, car fire scenario, modeling approach, and use of galvanization. Galvanization slightly delays and reduces peak temperature. Regarding the different models, CFD-FEM (CFD: computational fluid dynamics, FEM: finite-element method) coupled models predict lower temperatures than the Hasemi model, because the latter conservatively assumes that the fire flame continuously touches the ceiling. Further, the Hasemi model cannot account for the effect of reduced emissivity from galvanization on the absorbed heat flux. Detailed temperature distributions obtained in the steel members can be used to complete efficient structural fire designs based on the member sections, structure layout, and use of galvanization.

关键词: open car park     localized fire     steel frame     numerical modeling     computational fluid dynamics    

电动汽车市场加速发展

Chris Palmer

《工程(英文)》 2021年 第7卷 第2期   页码 136-138 doi: 10.1016/j.eng.2020.12.009

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

摘要: The current standard of care in hematological malignancies has brought considerable clinical benefits to patients. However, important bottlenecks still limit optimal achievements following a current medical practice. The genetic complexity of the diseases and the heterogeneity of tumor clones cause difficulty in ensuring long-term efficacy of conventional treatments for most hematological disorders. Consequently, new treatment strategies are necessary to improve clinical outcomes. Chimeric antigen receptor T-cell (CAR T) immunotherapy opens a new path for targeted therapy of hematological malignancies. In this review, through a representative case study, we summarize the current experience of CAR T-cell therapy, the management of common side effects, the causative mechanisms of therapy resistance, and new strategies to improve the efficacy of CAR T-cell therapy.

关键词: CAR T cells     hematological malignancies     review    

虚实融合的协同工作环境CAR-CA工程技术研究进展

赵沁平

《中国工程科学》 2009年 第11卷 第10期   页码 25-31

摘要: 面向我国自行设计生产商用大飞机的需求,在863计划支持下,正在研制用于驾驶舱布局设计和飞机关键部件辅助拆装维护的虚 实融合协同工作环境CAR-CA(collaborative augmented reality概要介绍CAR-CA的工程技术研究进展,包括体系结构、系统组成、关键技术研究和系统的应用前景等。

关键词: 虚实融合     协同工作     驾驶舱     设计     维护    

新冠病毒肺炎疫情肆虐——抗原检测能否挽救局面?

Peter Weiss

《工程(英文)》 2021年 第7卷 第1期   页码 3-5 doi: 10.1016/j.eng.2020.12.002

A fully solid-state cold thermal energy storage device for car seats using shape-memory alloys

《能源前沿(英文)》 2023年 第17卷 第4期   页码 504-515 doi: 10.1007/s11708-022-0855-3

摘要: Thermal energy storage has been a pivotal technology to fill the gap between energy demands and energy supplies. As a solid-solid phase change material, shape-memory alloys (SMAs) have the inherent advantages of leakage free, no encapsulation, negligible volume variation, as well as superior energy storage properties such as high thermal conductivity (compared with ice and paraffin) and volumetric energy density, making them excellent thermal energy storage materials. Considering these characteristics, the design of the shape-memory alloy based the cold thermal energy storage system for precooling car seat application is introduced in this paper based on the proposed shape-memory alloy-based cold thermal energy storage cycle. The simulation results show that the minimum temperature of the metal boss under the seat reaches 26.2 °C at 9.85 s, which is reduced by 9.8 °C, and the energy storage efficiency of the device is 66%. The influence of initial temperature, elastocaloric materials, and the shape-memory alloy geometry scheme on the performance of car seat cold thermal energy storage devices is also discussed. Since SMAs are both solid-state refrigerants and thermal energy storage materials, hopefully the proposed concept can promote the development of more promising shape-memory alloy-based cold and hot thermal energy storage devices.

关键词: shape-memory alloy (SMA)     elastocaloric effect (eCE)     cooled seat     cold thermal energy storage    

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

摘要: Chimeric antigen receptor (CAR) T cells have been indicated effective in treating B cell acute lymphoblastic leukemia and non-Hodgkin lymphoma and have shown encouraging results in preclinical and clinical studies. However, CAR T cells have achieved minimal success against solid malignancies because of the additional obstacles of their insufficient migration into tumors and poor amplification and persistence, in addition to antigen-negative relapse and an immunosuppressive microenvironment. Various preclinical studies are exploring strategies to overcome the above challenges. Mobilization of endogenous immune cells is also necessary for CAR T cells to obtain their optimal therapeutic effect given the importance of the innate immune responses in the elimination of malignant tumors. In this review, we focus on the recent advances in the engineering of CAR T cell therapies to restore the immune response in solid malignancies, especially with CAR T cells acting as cellular carriers to deliver immunomodulators to tumors to mobilize the endogenous immune response. We also explored the sensitizing effects of conventional treatment approaches, such as chemotherapy and radiotherapy, on CAR T cell therapy. Finally, we discuss the combination of CAR T cells with biomaterials or oncolytic viruses to enhance the anti-tumor outcomes of CAR T cell therapies in solid tumors.

关键词: CAR T cells     immunoregulatory molecules     endogenous immune response     solid malignancies    

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

摘要: Immune-based therapies have experienced a pronounced breakthrough in the past decades as they acquired multiple US Food and Drug Administration (FDA) approvals for various indications. To date, six chimeric antigen receptor T cell (CAR-T) therapies have been permitted for the treatment of certain patients with relapsed/refractory hematologic malignancies. However, several clinical trials of solid tumor CAR-T therapies were prematurely terminated, or they reported life-threatening treatment-related damages to healthy tissues. The simultaneous expression of target antigens by healthy organs and tumor cells is partly responsible for such toxicities. Alongside targeting tumor-specific antigens, targeting the aberrantly glycosylated glycoforms of tumor-associated antigens can also minimize the off-tumor effects of CAR-T therapies. Tn, T, and sialyl-Tn antigens have been reported to be involved in tumor progression and metastasis, and their expression results from the dysregulation of a series of glycosyltransferases and the endoplasmic reticulum protein chaperone, Cosmc. Moreover, these glycoforms have been associated with various types of cancers, including prostate, breast, colon, gastric, and lung cancers. Here, we discuss how underglycosylated antigens emerge and then detail the latest advances in the development of CAR-T-based immunotherapies that target some of such antigens.

关键词: cancer immunotherapy     chimeric antigen receptor     solid tumors     tumor-associated antigen     glycosylation     O-glycans     adoptive cell therapy    

发展共享汽车推动汽车强国建设

乔英俊,纪雪洪

《中国工程科学》 2018年 第20卷 第1期   页码 120-126 doi: 10.15302/J-SSCAE-2018.01.017

摘要:

本文介绍了共享汽车在国内外的发展现状与前景,并结合现阶段汽车发展的低碳化、电动化、网联化、智能化和共享化等新特征,着重对共享化推动汽车转型发展的影响进行了阐述。在此基础上,提出政府应将共享汽车放在汽车强国建设的战略高度,创造良好的发展环境,推动共享汽车在我国快速发展。

关键词: 共享汽车     汽车强国     问题     政策    

标题 作者 时间 类型 操作

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

Sabrina Wright, Conor Hennessy, Joanna Hester, Fadi Issa

期刊论文

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

李永红, 霍艳, 于雷, 王军志

期刊论文

基于自然杀伤细胞的癌症免疫疗法的进展和前景

胡渊, 田志刚, 张彩

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

中国私用轿车发展的现状与问题

郭孔辉

期刊论文

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

null

期刊论文

Thermal response of steel framing members in open car park fires

Xia YAN; Marion CHARLIER; Thomas GERNAY

期刊论文

电动汽车市场加速发展

Chris Palmer

期刊论文

CAR T-cell immunotherapy: a powerful weapon for fighting hematological B-cell malignancies

期刊论文

虚实融合的协同工作环境CAR-CA工程技术研究进展

赵沁平

期刊论文

新冠病毒肺炎疫情肆虐——抗原检测能否挽救局面?

Peter Weiss

期刊论文

A fully solid-state cold thermal energy storage device for car seats using shape-memory alloys

期刊论文

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

发展共享汽车推动汽车强国建设

乔英俊,纪雪洪

期刊论文