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基于 CAR-T 淋巴细胞的细胞治疗:机制验证、应用及自杀基因增强生物安全性:消解副作用的新机遇

英文原题:CAR-T lymphocyte-based cell therapies; mechanistic substantiation, applications and biosafety enhancement with suicide genes: new opportunities to melt side effects.

查看英文原题

CAR-T lymphocyte-based cell therapies; mechanistic substantiation, applications and biosafety enhancement with suicide genes: new opportunities to melt side effects.

PubMed 2024/07/18(内容时间) Front Immunol Q1 · IF 7(JCR 2025)

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中文摘要

免疫疗法通过检查点阻断抗体和过继性T细胞转移等策略在癌症治疗中取得了显著进展。CAR-T 细胞已成为一种有前景的方法,可结合这些策略并克服其局限性。本综述探讨了CAR-T 细胞作为一种活的药物用于癌症治疗。CAR-T 细胞是经过基因工程改造的免疫细胞,旨在通过识别特定抗原来靶向和消灭肿瘤细胞。

本研究涉及对CAR-T 细胞技术的全面文献综述,涵盖结构优化、代次、制造工艺和基因治疗策略。它考察了CAR-T 疗法在血液系统癌症和实体瘤中的应用,强调了挑战,并提出了一种基于自杀基因的机制以增强安全性。

结果显示CAR-T 技术取得了显著进步,尤其是在结构优化和代次方面。制造工艺已得到改进,以适用于更广泛的临床应用。然而,一系列固有挑战和副作用仍需解决。

总之,CAR-T 细胞在癌症治疗中具有巨大前景,但持续的研究对于提高肿瘤患者的疗效和安全性至关重要。所提出的基于自杀基因的机制为减轻副作用(包括细胞因子释放综合征——CAR-T 疗法最常见的毒性副作用——以及相关的神经毒性)提供了一种潜在的解决方案。

展开英文摘要原文

Immunotherapy has made significant strides in cancer treatment with strategies like checkpoint blockade antibodies and adoptive T cell transfer. Chimeric antigen receptor T cells (CAR-T) have emerged as a promising approach to combine these strategies and overcome their limitations. This review explores CAR-T cells as a living drug for cancer treatment. CAR-T cells are genetically engineered immune cells designed to target and eliminate tumor cells by recognizing specific antigens.

The study involves a comprehensive literature review on CAR-T cell technology, covering structure optimization, generations, manufacturing processes, and gene therapy strategies. It examines CAR-T therapy in haematologic cancers and solid tumors, highlighting challenges and proposing a suicide gene-based mechanism to enhance safety. The results show significant advancements in CAR-T technology, particularly in structure optimization and generation. The manufacturing process has improved for broader clinical application.

However, a series of inherent challenges and side effects still need to be addressed.

In conclusion, CAR-T cells hold great promise for cancer treatment, but ongoing research is crucial to improve efficacy and safety for oncology patients. The proposed suicide gene-based mechanism offers a potential solution to mitigate side effects including cytokine release syndrome (the most common toxic side effect of CAR-T therapy) and the associated neurotoxicity.

论文信息

作者
Ercilla-Rodríguez P、Sánchez-Díez M、Alegría-Aravena N、Quiroz-Troncoso J、Gavira-O'Neill CE、González-Martos R、Ramírez-Castillejo C
单位
ETSIAAB, Universidad Politécnica de Madrid, Madrid, Spain.Spain
文献类型
综述
期刊
Frontiers in immunology2024
原文标识
PubMed 39091493 · DOI 10.3389/fimmu.2024.1333150