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


ABSTRACT: 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.

SUBMITTER: Tang X 

PROVIDER: S-EPMC6713854 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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

Tang Xin X   Zhao Shasha S   Zhang Yang Y   Wang Yuelong Y   Zhang Zongliang Z   Yang Meijia M   Zhu Yanyu Y   Zhang Guanjie G   Guo Gang G   Tong Aiping A   Zhou Liangxue L  

Molecular therapy oncolytics 20190723


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 <i>  ...[more]

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