B7-H3 as a Target for CAR-T Cell Therapy in Skull Base Chordoma

Objectivechordomas are rare bone tumors with few therapeutic options. Skull base and sacrum are the two most common origin sites. Immunotherapies are emerging as the most promising approaches to fight various cancers. This study tends to identify new cell surface targets for immunotherapeutic option...

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Autores principales:	Cheng Long, Gaowei Li, Chengyun Zhang, Tao Jiang, Yanjun Li, Xin Duan, Gang Zhong
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	B7-H3 chordoma CAR-T cells skull base chordoma immunotherapy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/5a57d5834a2c47fe85e1b1e834f5dd6c
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spelling	oai:doaj.org-article:5a57d5834a2c47fe85e1b1e834f5dd6c2021-11-15T06:58:19ZB7-H3 as a Target for CAR-T Cell Therapy in Skull Base Chordoma2234-943X10.3389/fonc.2021.659662https://doaj.org/article/5a57d5834a2c47fe85e1b1e834f5dd6c2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.659662/fullhttps://doaj.org/toc/2234-943XObjectivechordomas are rare bone tumors with few therapeutic options. Skull base and sacrum are the two most common origin sites. Immunotherapies are emerging as the most promising approaches to fight various cancers. This study tends to identify new cell surface targets for immunotherapeutic options of skull base chordomas.Methodswe profiled 45 skull base chordoma clinical samples by immunohistochemistry for the expression of six CAR-Targets (PD-L1, B7-H3, B7-H4, VISTA, HER2 and HER3). In addition, we generated B7-H3 targeted CAR-T-cells and evaluated their antitumor activities in vitro.ResultsWe found that B7-H3 was positively stained in 7 out of 45 (16%) chordoma samples and established an expression hierarchy for these antigens (B7-H3 > HER3 > PD-L1 > HER2 = VISTA = B7-H4). We then generated a B7-H3 targeted CAR vector and demonstrated that B7-H3-CAR-T-cells recognized antigen positive cells and exhibited significant antitumor effects, including suppression of tumor spheroid formation, CAR-T-cell activation and cytokine secretion.ConclusionsOur results support B7-H3 might serve as a promising target for CAR-T-cell therapies against chordomas.Cheng LongGaowei LiChengyun ZhangTao JiangYanjun LiXin DuanGang ZhongFrontiers Media S.A.articleB7-H3chordomaCAR-T cellsskull base chordomaimmunotherapyNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	B7-H3 chordoma CAR-T cells skull base chordoma immunotherapy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	B7-H3 chordoma CAR-T cells skull base chordoma immunotherapy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Cheng Long Gaowei Li Chengyun Zhang Tao Jiang Yanjun Li Xin Duan Gang Zhong B7-H3 as a Target for CAR-T Cell Therapy in Skull Base Chordoma
description	Objectivechordomas are rare bone tumors with few therapeutic options. Skull base and sacrum are the two most common origin sites. Immunotherapies are emerging as the most promising approaches to fight various cancers. This study tends to identify new cell surface targets for immunotherapeutic options of skull base chordomas.Methodswe profiled 45 skull base chordoma clinical samples by immunohistochemistry for the expression of six CAR-Targets (PD-L1, B7-H3, B7-H4, VISTA, HER2 and HER3). In addition, we generated B7-H3 targeted CAR-T-cells and evaluated their antitumor activities in vitro.ResultsWe found that B7-H3 was positively stained in 7 out of 45 (16%) chordoma samples and established an expression hierarchy for these antigens (B7-H3 > HER3 > PD-L1 > HER2 = VISTA = B7-H4). We then generated a B7-H3 targeted CAR vector and demonstrated that B7-H3-CAR-T-cells recognized antigen positive cells and exhibited significant antitumor effects, including suppression of tumor spheroid formation, CAR-T-cell activation and cytokine secretion.ConclusionsOur results support B7-H3 might serve as a promising target for CAR-T-cell therapies against chordomas.
format	article
author	Cheng Long Gaowei Li Chengyun Zhang Tao Jiang Yanjun Li Xin Duan Gang Zhong
author_facet	Cheng Long Gaowei Li Chengyun Zhang Tao Jiang Yanjun Li Xin Duan Gang Zhong
author_sort	Cheng Long
title	B7-H3 as a Target for CAR-T Cell Therapy in Skull Base Chordoma
title_short	B7-H3 as a Target for CAR-T Cell Therapy in Skull Base Chordoma
title_full	B7-H3 as a Target for CAR-T Cell Therapy in Skull Base Chordoma
title_fullStr	B7-H3 as a Target for CAR-T Cell Therapy in Skull Base Chordoma
title_full_unstemmed	B7-H3 as a Target for CAR-T Cell Therapy in Skull Base Chordoma
title_sort	b7-h3 as a target for car-t cell therapy in skull base chordoma
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/5a57d5834a2c47fe85e1b1e834f5dd6c
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B7-H3 as a Target for CAR-T Cell Therapy in Skull Base Chordoma

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