Tang Xin, Zhao Shasha, Zhang Yang, Wang Yuelong, Zhang Zongliang, Yang Meijia, Zhu Yanyu, Zhang Guanjie, Guo Gang, Tong Aiping, Zhou Liangxue
Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, China.
State Key Laboratory of Biotherapy, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, China.
Mol Ther Oncolytics. 2019 Jul 23;14:279-287. doi: 10.1016/j.omto.2019.07.002. eCollection 2019 Sep 27.
Glioblastoma (GBM) remains one of the most malignant primary tumors in adults, with a 5-year survival rate less than 10% because of lacking effective treatment. Here, we aimed to explore whether B7-H3 could serve as a novel therapeutic target for GBM in chimeric antigen receptor (CAR) T cell therapy. In this study, a CAR targeting B7-H3 was constructed and transduced into T cells by lentivirus. Antitumor effects of B7-H3-specific CAR-T cells were assessed with primary and GBM cell lines both and . Our results indicated that B7-H3 was positively stained in most of the clinical glioma samples, and its expression levels were correlated to the malignancy grade and poor survival in both low-grade glioma (LGG) and GBM patients. Specific antitumor functions of CAR-T cells were confirmed by cytotoxic and ELISA assay both in primary glioblastoma cells and GBM cell lines. In the orthotropic GBM models, the median survival of the CAR-T-cell-treated group was significantly longer than that of the control group. In conclusion, B7-H3 is frequently overexpressed in GBM patients and may serve as a therapeutic target in CAR-T therapy.
胶质母细胞瘤（GBM）仍然是成人中最恶性的原发性肿瘤之一，由于缺乏有效的治疗方法，其5年生存率低于10%。在此，我们旨在探讨B7-H3是否可作为嵌合抗原受体（CAR）T细胞疗法中GBM的新型治疗靶点。在本研究中，构建了靶向B7-H3的CAR，并通过慢病毒将其转导至T细胞中。分别使用原发性和GBM细胞系评估B7-H3特异性CAR-T细胞的抗肿瘤作用。我们的结果表明，大多数临床胶质瘤样本中B7-H3呈阳性染色，其表达水平与低级别胶质瘤（LGG）和GBM患者的恶性程度及不良预后相关。在原发性胶质母细胞瘤细胞和GBM细胞系中，通过细胞毒性和ELISA检测均证实了CAR-T细胞的特异性抗肿瘤功能。在原位GBM模型中，CAR-T细胞治疗组的中位生存期显著长于对照组。总之，B7-H3在GBM患者中经常过度表达，可能作为CAR-T治疗的靶点。
