CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:CAR-T cell therapy in brain malignancies: obstacles in the face of cellular trafficking and persistence.
CAR-T cell therapy in brain malignancies: obstacles in the face of cellular trafficking and persistence.
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CAR-T(CAR-T)细胞疗法为治疗脑部恶性肿瘤提供了巨大前景,但其临床转化仍然有限。多形性胶质母细胞瘤(GBM)、弥漫性内生性桥脑胶质瘤(DIPG)和髓母细胞瘤(MB)等肿瘤预后差,对放疗、化疗和手术切除等常规治疗手段反应有限。CAR-T 细胞疗法在这些情况下的应用面临重大挑战,主要体现在细胞高效转运至肿瘤微环境以及进入异质性肿瘤区域方面。此外,CAR-T 细胞持久性,即输注细胞的长期存活和功能,仍然是实现持久治疗反应和防止肿瘤复发的关键障碍。本综述旨在通过讨论限制CAR-T 细胞在脑肿瘤中疗效的潜在机制、回顾当前旨在克服这些挑战的策略,以及评估增强CAR-T 疗法在此背景下有效性的新方法,来解决转运和持久性这两大主要障碍。
Chimeric Antigen Receptor T (CAR-T) cell therapy offers substantial promise for the treatment of brain malignancies, yet its clinical translation remains limited. Tumors such as Glioblastoma Multiforme (GBM), Diffuse Intrinsic Pontine Glioma (DIPG), and Medulloblastoma (MB) are associated with poor prognoses and exhibit limited responsiveness to conventional treatment modalities, including radiotherapy, chemotherapy, and surgical resection.
The application of CAR-T cell therapy in these contexts faces significant challenges, primarily in terms of efficient cellular trafficking into the tumor microenvironment and access to heterogeneous tumor regions.
Furthermore, CAR-T cell persistence, defined by the long-term survival and functionality of infused cells, remains a critical hurdle in achieving durable therapeutic responses and preventing tumor relapses. This review aims to address the two predominant barriers, trafficking and persistence, by discussing the underlying mechanisms that limit CAR-T cell efficacy in brain tumors, reviewing current strategies aimed at overcoming these challenges, and evaluating novel approaches to enhance the effectiveness of CAR-T therapies in this setting.
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