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:GD2 CAR T cells against human glioblastoma.
GD2 CAR T cells against human glioblastoma.
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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。
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.
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