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 in vitro and in vivo. 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肿瘤之一，由于缺乏有效的治疗方法，其5年生存率不到10％。在这里，我们旨在探讨B7-H3是否可以作为嵌合抗原受体（CAR）T细胞疗法中GBM的新型治疗靶标。在这项研究中，构建了靶向B7-H3的CAR，并通过慢病毒将其转导到T细胞中。在体外和体内均用原代和GBM细胞系评估了B7-H3特异性CAR-T细胞的抗肿瘤作用。我们的结果表明，在大多数临床神经胶质瘤样本中，B7-H3呈阳性染色，其表达水平与低度神经胶质瘤（LGG）和GBM患者的恶性程度和不良的生存率相关。通过原代胶质母细胞瘤细胞和GBM细胞系的细胞毒性和ELISA分析证实了CAR-T细胞的特异性抗肿瘤功能。在正交各向异性GBM模型中，CAR-T细胞治疗组的中位生存期显着长于对照组。总之，B7-H3在GBM患者中经常过表达，并且可以作为CAR-T治疗的治疗靶标。