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实体瘤和血液系统恶性肿瘤中CAR-T细胞疗法的先进策略

Advanced Strategies of CAR-T Cell Therapy in Solid Tumors and Hematological Malignancies.

作者信息

Liu Yangjie, Peng Cao, Ahad Faiza, Ali Zaidi Syed Aqib, Muluh Tobias Achu, Fu Qiuxia

机构信息

Department of Pharmacy, Luzhou People's Hospital, Luzhou 646000, Sichuan, PRC China.

Department of Pharmacy, Luzhou People's Hospital, Luzhou 646000, Sichuan PRC China.

出版信息

Recent Pat Anticancer Drug Discov. 2024;19(5):557-572. doi: 10.2174/0115748928277331231218115402.

Abstract

Chimeric antigen receptor T-cells, known as CAR-T cells, represent a promising breakthrough in the realm of adoptive cell therapy. These T-cells are genetically engineered to carry chimeric antigen receptors that specifically target tumors. They have achieved notable success in the treatment of blood-related cancers, breathing new life into this field of medical research. However, numerous obstacles limit chimeric antigen receptors T-cell therapy's efficacy, such as it cannot survive in the body long. It is prone to fatigue and exhaustion, leading to difficult tumor elimination and repeated recurrence, affecting solid tumors and hematological malignancies. The challenges posed by solid tumors, especially in the context of the complex solid-tumor microenvironment, require specific strategies. This review outlines recent advancements in improving chimeric antigen receptors T-cell therapy by focusing on the chimeric antigen receptors protein, modifying T-cells, and optimizing the interaction between T-cells and other components within the tumor microenvironment. This article aims to provide an extensive summary of the latest discoveries regarding CAR-T cell therapy, encompassing its application across various types of human cancers. Moreover, it will delve into the obstacles that have emerged in recent times, offering insights into the challenges faced by this innovative approach. Finally, it highlights novel therapeutic options in treating hematological and solid malignancies with chimeric antigen receptors T-cell therapies.

摘要

嵌合抗原受体T细胞(Chimeric antigen receptor T-cells,简称CAR-T细胞)是过继性细胞疗法领域一项颇具前景的突破。这些T细胞经过基因工程改造,携带能够特异性靶向肿瘤的嵌合抗原受体。它们在血液系统癌症的治疗中取得了显著成功,为这一医学研究领域注入了新的活力。然而,诸多障碍限制了嵌合抗原受体T细胞疗法的疗效,比如其在体内无法长期存活,容易出现耗竭,导致肿瘤难以清除且反复复发,对实体瘤和血液系统恶性肿瘤均有影响。实体瘤带来的挑战,尤其是在复杂的实体瘤微环境背景下,需要特定的策略。本综述通过聚焦嵌合抗原受体蛋白、改造T细胞以及优化T细胞与肿瘤微环境中其他成分之间的相互作用,概述了在改进嵌合抗原受体T细胞疗法方面的最新进展。本文旨在全面总结关于CAR-T细胞疗法的最新发现,包括其在各类人类癌症中的应用。此外,还将深入探讨近期出现的障碍,洞察这一创新疗法所面临的挑战。最后,强调了用嵌合抗原受体T细胞疗法治疗血液系统和实体恶性肿瘤的新型治疗选择。

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