5T4-specific chimeric antigen receptor modification promotes the immune efficacy of cytokine-induced killer cells against nasopharyngeal carcinoma stem cell-like cells

Abstract Relapse and metastasis of nasopharyngeal carcinoma (NPC) are presumably attributed to cancer stem cells (CSCs). In recent years, chimeric antigen receptor (CAR)-modified immune effector cells have been shown to have impressive antitumour efficacy. In this study, we aimed to identify appropr...

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Autores principales:	Xueyang Guo, Hang Zheng, Weiren Luo, Qianbing Zhang, Jingxian Liu, Kaitai Yao
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cc3fd02a8bce4d298f3628c81f2bb877
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spelling	oai:doaj.org-article:cc3fd02a8bce4d298f3628c81f2bb8772021-12-02T12:32:02Z5T4-specific chimeric antigen receptor modification promotes the immune efficacy of cytokine-induced killer cells against nasopharyngeal carcinoma stem cell-like cells10.1038/s41598-017-04756-92045-2322https://doaj.org/article/cc3fd02a8bce4d298f3628c81f2bb8772017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04756-9https://doaj.org/toc/2045-2322Abstract Relapse and metastasis of nasopharyngeal carcinoma (NPC) are presumably attributed to cancer stem cells (CSCs). In recent years, chimeric antigen receptor (CAR)-modified immune effector cells have been shown to have impressive antitumour efficacy. In this study, we aimed to identify appropriate tumour-associated antigens predominantly expressed on NPC stem cells (NPCSCs) and determine their suitability for CAR-engineered cytokine-induced killer (CIK) cell therapy against NPC. By investigating the expression patterns of potential target antigens (ROR1, 5T4 and CAIX) in NPC, we found that the oncofetal antigen 5T4 was predominately expressed in NPC cell lines and tissues but absent in non-cancerous nasopharyngeal tissues. Moreover, significantly enhanced expression of 5T4 in NPC spheroids revealed its relationship with putative NPCSCs. Hence, we designed a CAR construct (5T4-28Z) specific for 5T4 and generated CAR-transduced CIK cells. Our results showed that the artificial CAR was efficiently expressed on the surface of CIK cells and that no native phenotypes were altered by the gene transduction. Functional assays revealed that 5T4-28Z-CIK cells possessed both CAR-mediated and CAR-independent anti-NPC activity and were capable of efficiently attacking NPC cells, especially NPCSC-like cells in vitro, suggesting that they might serve as an attractive tool for developing efficient therapies against NPC.Xueyang GuoHang ZhengWeiren LuoQianbing ZhangJingxian LiuKaitai YaoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Xueyang Guo Hang Zheng Weiren Luo Qianbing Zhang Jingxian Liu Kaitai Yao 5T4-specific chimeric antigen receptor modification promotes the immune efficacy of cytokine-induced killer cells against nasopharyngeal carcinoma stem cell-like cells
description	Abstract Relapse and metastasis of nasopharyngeal carcinoma (NPC) are presumably attributed to cancer stem cells (CSCs). In recent years, chimeric antigen receptor (CAR)-modified immune effector cells have been shown to have impressive antitumour efficacy. In this study, we aimed to identify appropriate tumour-associated antigens predominantly expressed on NPC stem cells (NPCSCs) and determine their suitability for CAR-engineered cytokine-induced killer (CIK) cell therapy against NPC. By investigating the expression patterns of potential target antigens (ROR1, 5T4 and CAIX) in NPC, we found that the oncofetal antigen 5T4 was predominately expressed in NPC cell lines and tissues but absent in non-cancerous nasopharyngeal tissues. Moreover, significantly enhanced expression of 5T4 in NPC spheroids revealed its relationship with putative NPCSCs. Hence, we designed a CAR construct (5T4-28Z) specific for 5T4 and generated CAR-transduced CIK cells. Our results showed that the artificial CAR was efficiently expressed on the surface of CIK cells and that no native phenotypes were altered by the gene transduction. Functional assays revealed that 5T4-28Z-CIK cells possessed both CAR-mediated and CAR-independent anti-NPC activity and were capable of efficiently attacking NPC cells, especially NPCSC-like cells in vitro, suggesting that they might serve as an attractive tool for developing efficient therapies against NPC.
format	article
author	Xueyang Guo Hang Zheng Weiren Luo Qianbing Zhang Jingxian Liu Kaitai Yao
author_facet	Xueyang Guo Hang Zheng Weiren Luo Qianbing Zhang Jingxian Liu Kaitai Yao
author_sort	Xueyang Guo
title	5T4-specific chimeric antigen receptor modification promotes the immune efficacy of cytokine-induced killer cells against nasopharyngeal carcinoma stem cell-like cells
title_short	5T4-specific chimeric antigen receptor modification promotes the immune efficacy of cytokine-induced killer cells against nasopharyngeal carcinoma stem cell-like cells
title_full	5T4-specific chimeric antigen receptor modification promotes the immune efficacy of cytokine-induced killer cells against nasopharyngeal carcinoma stem cell-like cells
title_fullStr	5T4-specific chimeric antigen receptor modification promotes the immune efficacy of cytokine-induced killer cells against nasopharyngeal carcinoma stem cell-like cells
title_full_unstemmed	5T4-specific chimeric antigen receptor modification promotes the immune efficacy of cytokine-induced killer cells against nasopharyngeal carcinoma stem cell-like cells
title_sort	5t4-specific chimeric antigen receptor modification promotes the immune efficacy of cytokine-induced killer cells against nasopharyngeal carcinoma stem cell-like cells
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/cc3fd02a8bce4d298f3628c81f2bb877
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5T4-specific chimeric antigen receptor modification promotes the immune efficacy of cytokine-induced killer cells against nasopharyngeal carcinoma stem cell-like cells

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