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

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...

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Autores principales: Tang, Xin, Zhao, Shasha, Zhang, Yang, Wang, Yuelong, Zhang, Zongliang, Yang, Meijia, Zhu, Yanyu, Zhang, Guanjie, Guo, Gang, Tong, Aiping, Zhou, Liangxue
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6713854/
https://www.ncbi.nlm.nih.gov/pubmed/31485480
http://dx.doi.org/10.1016/j.omto.2019.07.002
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author Tang, Xin
Zhao, Shasha
Zhang, Yang
Wang, Yuelong
Zhang, Zongliang
Yang, Meijia
Zhu, Yanyu
Zhang, Guanjie
Guo, Gang
Tong, Aiping
Zhou, Liangxue
author_facet Tang, Xin
Zhao, Shasha
Zhang, Yang
Wang, Yuelong
Zhang, Zongliang
Yang, Meijia
Zhu, Yanyu
Zhang, Guanjie
Guo, Gang
Tong, Aiping
Zhou, Liangxue
author_sort Tang, Xin
collection PubMed
description 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.
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spelling pubmed-67138542019-09-04 B7-H3 as a Novel CAR-T Therapeutic Target for Glioblastoma Tang, Xin Zhao, Shasha Zhang, Yang Wang, Yuelong Zhang, Zongliang Yang, Meijia Zhu, Yanyu Zhang, Guanjie Guo, Gang Tong, Aiping Zhou, Liangxue Mol Ther Oncolytics Article 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. American Society of Gene & Cell Therapy 2019-07-23 /pmc/articles/PMC6713854/ /pubmed/31485480 http://dx.doi.org/10.1016/j.omto.2019.07.002 Text en © 2019 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Tang, Xin
Zhao, Shasha
Zhang, Yang
Wang, Yuelong
Zhang, Zongliang
Yang, Meijia
Zhu, Yanyu
Zhang, Guanjie
Guo, Gang
Tong, Aiping
Zhou, Liangxue
B7-H3 as a Novel CAR-T Therapeutic Target for Glioblastoma
title B7-H3 as a Novel CAR-T Therapeutic Target for Glioblastoma
title_full B7-H3 as a Novel CAR-T Therapeutic Target for Glioblastoma
title_fullStr B7-H3 as a Novel CAR-T Therapeutic Target for Glioblastoma
title_full_unstemmed B7-H3 as a Novel CAR-T Therapeutic Target for Glioblastoma
title_short B7-H3 as a Novel CAR-T Therapeutic Target for Glioblastoma
title_sort b7-h3 as a novel car-t therapeutic target for glioblastoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6713854/
https://www.ncbi.nlm.nih.gov/pubmed/31485480
http://dx.doi.org/10.1016/j.omto.2019.07.002
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