B7-H3 as a Novel CAR-T Therapeutic Target for Glioblastoma

• Main Authors: Xin Tang, Shasha Zhao, Yang Zhang, Yuelong Wang, Zongliang Zhang, Meijia Yang, Yanyu Zhu, Guanjie Zhang, Gang Guo, Aiping Tong, Liangxue Zhou
• Format: Article
• Language: English
• Published: Elsevier 2019-09-01
• Series: Molecular Therapy: Oncolytics
• Online Access: http://www.sciencedirect.com/science/article/pii/S2372770519300683

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. Keywords: B7-H3, chimeric antigen receptor, glioblastoma, low grade glioma, immunotherapy