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.
CAR-T(CAR-T)细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Suppressive immune microenvironment and CART therapy for glioblastoma: Future prospects and challenges.
Suppressive immune microenvironment and CART therapy for glioblastoma: Future prospects and challenges.
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胶质母细胞瘤是一种高度恶性的颅内肿瘤,其治疗进展缓慢。既往涉及靶向治疗和免疫检查点抑制剂的临床试验在治疗胶质母细胞瘤方面未显示出显著获益。这种无效性在很大程度上归因于胶质母细胞瘤复杂的免疫抑制环境。胶质母细胞瘤细胞表现出低免疫原性和强异质性,且免疫微环境中充满抑制性细胞因子、大量免疫抑制细胞以及不足的有效T细胞。幸运的是,近期针对胶质母细胞瘤的CAR-T 治疗I期临床试验已证实其安全性,少数患者获得了生存获益。然而,CAR-T 治疗仍面临挑战,包括血脑屏障阻碍、抗原丢失以及免疫抑制性肿瘤微环境(TME)。本文从肿瘤细胞内在和外在因素两方面详细探讨了胶质母细胞瘤的免疫微环境,综述了当前关于多靶点CAR-T 治疗的临床和基础研究,并在最后概述了使用CAR-T 细胞治疗胶质母细胞瘤的关键挑战。
Glioblastoma, a highly malignant intracranial tumor, has acquired slow progress in treatment. Previous clinical trials involving targeted therapy and immune checkpoint inhibitors have shown no significant benefits in treating glioblastoma. This ineffectiveness is largely due to the complex immunosuppressive environment of glioblastoma.
Glioblastoma cells exhibit low immunogenicity and strong heterogeneity and the immune microenvironment is replete with inhibitory cytokines, numerous immunosuppressive cells, and insufficient effective T cells. Fortunately, recent Phase I clinical trials of CART therapy for glioblastoma have confirmed its safety, with a small subset of patients achieving survival benefits.
However, CART therapy continues to face challenges, including blood-brain barrier obstruction, antigen loss, and an immunosuppressive tumor microenvironment (TME). This article provides a detailed examination of glioblastoma's immune microenvironment, both from intrinsic and extrinsic tumor cell factors, reviews current clinical and basic research on multi-targets CART treatment, and concludes by outlining the key challenges in using CART cells for glioblastoma therapy.
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