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胶质母细胞瘤的嵌合抗原受体T细胞疗法:临床试验首个十年综述

CAR T cell therapy for glioblastoma: A review of the first decade of clinical trials.

作者信息

Begley Sabrina L, O'Rourke Donald M, Binder Zev A

机构信息

GBM Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104, USA; Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

GBM Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104, USA; Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

出版信息

Mol Ther. 2025 Jun 4;33(6):2454-2461. doi: 10.1016/j.ymthe.2025.03.004. Epub 2025 Mar 8.


DOI:10.1016/j.ymthe.2025.03.004
PMID:40057825
Abstract

Glioblastoma (GBM) is an aggressive primary brain tumor with a poor prognosis and few effective treatment options. Focus has shifted toward using immunotherapies, such as chimeric antigen receptor (CAR) T cells, to selectively target tumor antigens and mediate cytotoxic activity within an otherwise immunosuppressive tumor microenvironment. Between 2015 and 2024, the results of eight completed and two ongoing phase I clinical trials have been published. The majority of studies have treated recurrent GBM patients, although the inter- and intra-patient tumor heterogeneity has been historically challenging to overcome. Molecular targets have included EGFR, HER2, and IL13Rα2 and there has been continued development in improving receptor constructs, identifying novel targets, and adding adjuvant enhancers to increase efficacy. CAR T cells have been safely administered through both peripheral and locoregional routes but with variable clinical and radiographic efficacy. Most trials utilized autologous T cell products to avoid immune rejection yet were unable to consistently show robust engraftment and persistence within patients. Nonetheless, targeted immunotherapies such as CAR T cell therapy remain the next frontier for GBM treatment, and the popularity and complexity of this undertaking is evident in the past, present, and future landscape of clinical trials.

摘要

胶质母细胞瘤(GBM)是一种侵袭性原发性脑肿瘤,预后较差,有效治疗选择有限。研究重点已转向使用免疫疗法,如嵌合抗原受体(CAR)T细胞,以选择性地靶向肿瘤抗原,并在原本免疫抑制的肿瘤微环境中介导细胞毒性活性。2015年至2024年间,已发表了八项已完成和两项正在进行的I期临床试验结果。大多数研究治疗的是复发性GBM患者,尽管患者间和患者内肿瘤异质性一直是历史上难以克服的挑战。分子靶点包括表皮生长因子受体(EGFR)、人表皮生长因子受体2(HER2)和白细胞介素13受体α2(IL13Rα2),并且在改进受体构建体、确定新靶点以及添加辅助增强剂以提高疗效方面一直在持续发展。CAR T细胞已通过外周和局部区域途径安全给药,但临床和影像学疗效各不相同。大多数试验使用自体T细胞产品以避免免疫排斥,但未能始终如一地显示出在患者体内强大的植入和持久性。尽管如此,诸如CAR T细胞疗法等靶向免疫疗法仍然是GBM治疗的下一个前沿领域,并且这项工作的受欢迎程度和复杂性在过去、现在和未来的临床试验格局中都很明显。

相似文献

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引用本文的文献

[1]
Emerging trends in cell-based therapies: contemporary advances and ethical considerations in translational neurosurgical oncology.

J Neurooncol. 2025-7-22

本文引用的文献

[1]
CAR T Cells and T-Cell Therapies for Cancer: A Translational Science Review.

JAMA. 2024-12-10

[2]
Armored bicistronic CAR T cells with dominant-negative TGF-β receptor II to overcome resistance in glioblastoma.

Mol Ther. 2024-10-2

[3]
CAR T cell combination therapies to treat cancer.

Cancer Cell. 2024-8-12

[4]
IL-13Rα2/TGF-β bispecific CAR-T cells counter TGF-β-mediated immune suppression and potentiate anti-tumor responses in glioblastoma.

Neuro Oncol. 2024-10-3

[5]
Intrathecal bivalent CAR T cells targeting EGFR and IL13Rα2 in recurrent glioblastoma: phase 1 trial interim results.

Nat Med. 2024-5

[6]
Intraventricular CARv3-TEAM-E T Cells in Recurrent Glioblastoma.

N Engl J Med. 2024-4-11

[7]
Locoregional delivery of IL-13Rα2-targeting CAR-T cells in recurrent high-grade glioma: a phase 1 trial.

Nat Med. 2024-4

[8]
Repeated peripheral infusions of anti-EGFRvIII CAR T cells in combination with pembrolizumab show no efficacy in glioblastoma: a phase 1 trial.

Nat Cancer. 2024-3

[9]
CAR T cell therapy for patients with solid tumours: key lessons to learn and unlearn.

Nat Rev Clin Oncol. 2024-1

[10]
Glioblastoma Immunotherapy: A Systematic Review of the Present Strategies and Prospects for Advancements.

Int J Mol Sci. 2023-10-10

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