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通过下一代 CAR-T 细胞疗法解析胶质母细胞瘤中修饰 T 细胞受体:现状与未来挑战

英文原题:Unravelling the modified T cell receptor through Gen-Next CAR T cell therapy in Glioblastoma: Current status and future challenges.

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Unravelling the modified T cell receptor through Gen-Next CAR T cell therapy in Glioblastoma: Current status and future challenges.

PubMed 2025/03/20(内容时间) Biomed Pharmacother

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中文摘要

尽管胶质瘤治疗技术近期取得进展,手术、化疗和联合放疗等治疗方式仍可用于迅速缓解症状;这些治疗利用胶质瘤本身的异常特征发挥作用。此外,靶抗原数量较少、抗原异质性和免疫逃逸,可能是开发靶向治疗的原因之一。这一肿瘤学里程碑推动了针对胶质母细胞瘤的免疫疗法研发,以改善总生存期并治愈高级别胶质瘤患者。下一代 CAR-T 细胞疗法是一种有效免疫治疗策略,通过改造自体 T 细胞,使其表达针对胶质母细胞瘤的受体并调节细胞毒作用。

本综述考察 CAR-T 细胞疗法的临床前和临床结局及其局限,并介绍改善其功能的前沿技术和联合治疗可能性。发现:目前多种 CAR-T 疗法正在针对胶质母细胞瘤和其他脑部恶性肿瘤开展临床试验,多项临床前研究也显示出令人鼓舞的结果。

CAR-T 细胞疗法代表实体瘤治疗的一种有前景范式,但血脑屏障(BBB)、抗原逃逸、肿瘤微环境(TME)、肿瘤异质性及肿瘤可塑性等因素会抑制免疫应答,削弱疗法作用。仍需进一步研究准确识别靶点,并构建能反映胶质母细胞瘤相似结构的模型,以优化 CAR-T 疗效,筛选最可能从免疫治疗中获益的患者。

展开英文摘要原文

Despite current technological advancements in the treatment of glioma, immediate alleviation of symptoms can be catered by therapeutic modalities, including surgery, chemotherapy, and combinatorial radiotherapy that exploit aberrations of glioma. Additionally, a small number of target antigens, their heterogeneity, and immune evasion are the potential reasons for developing targeted therapies. This oncologic milestone has catalyzed interest in developing immunotherapies against Glioblastoma to improve overall survival and cure patients with high-grade glioma. The next-gen CAR-T Cell therapy is one of the effective immunotherapeutic strategies in which autologous T cells have been modified to express receptors against GBM and it modulates cytotoxicity.

In this review article, we examine preclinical and clinical outcomes, and limitations as well as present cutting-edge techniques to improve the function of CAR-T cell therapy and explore the possibility of combination therapy.

To date, several CAR T-cell therapies are being evaluated in clinical trials for GBM and other brain malignancies and multiple preclinical studies have demonstrated encouraging outcomes. IMPLICATIONS: CAR-T cell therapy represents a promising therapeutic paradigm in the treatment of solid tumors but a few limitations include, the blood-brain barrier (BBB), antigen escape, tumor microenvironment (TME), tumor heterogeneity, and its plasticity that suppresses immune responses weakens the ability of this therapy. Additional investigation is required that can accurately identify the targets and reflect the similar architecture of glioblastoma, thus optimizing the efficiency of CAR-T cell therapy; allowing for the selection of patients most likely to benefit from immuno-based treatments.

论文信息

作者
Bhutani B、Sharma V、Ganguly NK、Rana R
第一作者单位
Department of Biotechnology and Research, Sir Ganga Ram Hospital, New Delhi 110060, India.India
通讯作者单位
Department of Biotechnology and Research, Sir Ganga Ram Hospital, New Delhi 110060, India. Electronic address: rashmi.rana@sgrh.com.India
文献类型
综述
期刊
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie2025 May
原文标识
PubMed 40117901 · DOI 10.1016/j.biopha.2025.117987