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嵌合抗原受体T细胞:概念、应用、局限性及建议解决方案概述

Chimeric Antigen Receptor T-Cells: An Overview of Concepts, Applications, Limitations, and Proposed Solutions.

作者信息

Alnefaie Alaa, Albogami Sarah, Asiri Yousif, Ahmad Tanveer, Alotaibi Saqer S, Al-Sanea Mohammad M, Althobaiti Hisham

机构信息

Department of Medical Services, King Faisal Medical Complex, Taif, Saudi Arabia.

Department of Biotechnology, College of Science, Taif University, Taif, Saudi Arabia.

出版信息

Front Bioeng Biotechnol. 2022 Jun 22;10:797440. doi: 10.3389/fbioe.2022.797440. eCollection 2022.

Abstract

Adaptive immunity, orchestrated by B-cells and T-cells, plays a crucial role in protecting the body from pathogenic invaders and can be used as tools to enhance the body's defense mechanisms against cancer by genetically engineering these immune cells. Several strategies have been identified for cancer treatment and evaluated for their efficacy against other diseases such as autoimmune and infectious diseases. One of the most advanced technologies is chimeric antigen receptor (CAR) T-cell therapy, a pioneering therapy in the oncology field. Successful clinical trials have resulted in the approval of six CAR-T cell products by the Food and Drug Administration for the treatment of hematological malignancies. However, there have been various obstacles that limit the use of CAR T-cell therapy as the first line of defense mechanism against cancer. Various innovative CAR-T cell therapeutic designs have been evaluated in preclinical and clinical trial settings and have demonstrated much potential for development. Such trials testing the suitability of CARs against solid tumors and HIV are showing promising results. In addition, new solutions have been proposed to overcome the limitations of this therapy. This review provides an overview of the current knowledge regarding this novel technology, including CAR T-cell structure, different applications, limitations, and proposed solutions.

摘要

由B细胞和T细胞精心调控的适应性免疫在保护身体免受病原体侵袭方面发挥着关键作用,并且可以通过对这些免疫细胞进行基因工程改造,将其用作增强机体抗癌防御机制的工具。已经确定了几种癌症治疗策略,并对其针对自身免疫性疾病和传染病等其他疾病的疗效进行了评估。最先进的技术之一是嵌合抗原受体(CAR)T细胞疗法,这是肿瘤学领域的一种开创性疗法。成功的临床试验使得六种CAR-T细胞产品获得美国食品药品监督管理局批准,用于治疗血液系统恶性肿瘤。然而,存在各种障碍限制了CAR T细胞疗法作为抗癌第一道防线的应用。在临床前和临床试验环境中对各种创新的CAR-T细胞治疗设计进行了评估,这些设计已显示出很大的发展潜力。此类测试CARs对实体瘤和HIV适用性的试验正显示出有希望的结果。此外,已经提出了新的解决方案来克服这种疗法的局限性。本综述概述了关于这项新技术的当前知识,包括CAR T细胞结构、不同应用、局限性和提出的解决方案。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5b3/9256991/dc7915c3055b/fbioe-10-797440-g001.jpg

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