← 返回

靶向人胶质母细胞瘤的 GD2 CAR-T 细胞

英文原题:GD2 CAR T cells against human glioblastoma.

查看英文原题

GD2 CAR T cells against human glioblastoma.

PubMed 2021/10/27(内容时间) NPJ Precis Oncol Q1 · IF 9.9(JCR 2025)

分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。

中文摘要

胶质母细胞瘤是最具恶性的原发性脑肿瘤,目前仍需要有效的医学治疗。我们分离了患者来源的胶质母细胞瘤细胞,其显示高 GD2 抗原表达,代表 CAR-T 策略的潜在靶点。数据强调了 GD2 CAR 在 2D 和 3D 胶质母细胞瘤模型中具有强大的抗肿瘤潜力,并伴随选定的细胞因子显著且 CAR-T 限制性增加。有趣的是,在所有共培养物中表达的免疫抑制剂 TGF 1 并未影响抗肿瘤活性。使用原代胶质母细胞瘤细胞的正位 NOD/SCID 模型再现了人类组织病理学特征。考虑到关于靶向脑肿瘤递送途径的数据仍存在矛盾,我们比较了脑内与静脉 CAR-T 注射。我们报告,脑内途径以剂量依赖性方式显著延长了生存时间,且没有任何副作用。总体而言,所提出的抗 GD2 CAR 可以对抗人类胶质母细胞瘤,可能为一种仍无法治愈的癌症开辟新的治疗选择。

展开英文摘要原文

Glioblastoma is the most malignant primary brain tumor and is still in need of effective medical treatment.

We isolated patient-derived glioblastoma cells showing high GD2 antigen expression representing a potential target for CAR T strategy. Data highlighted a robust GD2 CAR antitumor potential in 2D and 3D glioblastoma models associated with a significant and CAR T-restricted increase of selected cytokines.

Interestingly, immunosuppressant TGF 1, expressed in all co-cultures, did not influence antitumor activity. The orthotopic NOD/SCID models using primary glioblastoma cells reproduced human histopathological features. Considering still-conflicting data on the delivery route for targeting brain tumors, we compared intracerebral versus intravenous CAR T injections.

We report that the intracerebral route significantly increased the length of survival time in a dose-dependent manner, without any side effects. Collectively, the proposed anti-GD2 CAR can counteract human glioblastoma potentially opening a new therapeutic option for a still incurable cancer.

论文信息

作者
Prapa M、Chiavelli C、Golinelli G、Grisendi G、Bestagno M、Di Tinco R、Dall'Ora M、Neri G
第一作者单位
Laboratory of Cellular Therapy, Division of Oncology, Department of Medical and Surgical Sciences for Children & Adults, University of Modena and Reggio Emilia, Modena, Italy.Italy
通讯作者单位
Laboratory of Cellular Therapy, Division of Oncology, Department of Medical and Surgical Sciences for Children & Adults, University of Modena and Reggio Emilia, Modena, Italy. massimo.dominici@unimore.it.Italy
期刊
NPJ precision oncology2021 Oct 27
原文标识
PubMed 34707200 · DOI 10.1038/s41698-021-00233-9