HER2-specific chimeric antigen receptor-T cells for targeted therapy of metastatic colorectal cancer

Abstract Chimeric antigen receptor (CAR) - T cell therapy is a new class of cellular immunotherapies, which has made great achievements in the treatment of malignant tumors. Despite improvements in colorectal cancer (CRC) therapy, treatment of many patients fails because of metastasis and recurrence...

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Autores principales:	Jie Xu, Qingtao Meng, Hao Sun, Xinwei Zhang, Jun Yun, Bin Li, Shenshen Wu, Xiaobo Li, Hongbao Yang, Haitao Zhu, Michael Aschner, Michela Relucenti, Giuseppe Familiari, Rui Chen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Publishing Group 2021
Materias:	Cytology QH573-671
Acceso en línea:	https://doaj.org/article/a951c8fcb43d4002b7844f3a23348587
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spelling	oai:doaj.org-article:a951c8fcb43d4002b7844f3a233485872021-11-28T12:04:20ZHER2-specific chimeric antigen receptor-T cells for targeted therapy of metastatic colorectal cancer10.1038/s41419-021-04100-02041-4889https://doaj.org/article/a951c8fcb43d4002b7844f3a233485872021-11-01T00:00:00Zhttps://doi.org/10.1038/s41419-021-04100-0https://doaj.org/toc/2041-4889Abstract Chimeric antigen receptor (CAR) - T cell therapy is a new class of cellular immunotherapies, which has made great achievements in the treatment of malignant tumors. Despite improvements in colorectal cancer (CRC) therapy, treatment of many patients fails because of metastasis and recurrence. The human epidermal growth factor receptor 2 (HER2) is a substantiated target for CAR-T therapy, and has been reported recently to be over-expressed in CRC, which may provide a potential therapeutic target for CRC treatment. Herein, HER2 was a promising target of metastatic colorectal cancer (mCRC) in CAR-T therapy as assessed by flow cytometry and tissue microarray (TMA) with 9-year survival follow-up data. Furthermore, HER2-specific CAR-T cells exhibited strong cytotoxicity and cytokine-secreting ability against CRC cells in vitro. Moreover, through the tumor-bearing model of the NOD-Prkdcem26cd52Il2rgem26Cd22/Nju (NCG) mice, HER2 CAR-T cells showed signs of effectively preventing CRC progression in three different xenograft models. Notably, HER2 CAR-T cells displayed greater aggressiveness in HER2+ CRC in the patient-derived tumor xenograft (PDX) models and had potent immunotherapeutic capacity for mCRC in the metastatic xenograft mouse models. In conclusion, our studies provide scientific evidence that HER2 CAR-T cells represent an emerging immunotherapy for the treatment of mCRC.Jie XuQingtao MengHao SunXinwei ZhangJun YunBin LiShenshen WuXiaobo LiHongbao YangHaitao ZhuMichael AschnerMichela RelucentiGiuseppe FamiliariRui ChenNature Publishing GrouparticleCytologyQH573-671ENCell Death and Disease, Vol 12, Iss 12, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cytology QH573-671
spellingShingle	Cytology QH573-671 Jie Xu Qingtao Meng Hao Sun Xinwei Zhang Jun Yun Bin Li Shenshen Wu Xiaobo Li Hongbao Yang Haitao Zhu Michael Aschner Michela Relucenti Giuseppe Familiari Rui Chen HER2-specific chimeric antigen receptor-T cells for targeted therapy of metastatic colorectal cancer
description	Abstract Chimeric antigen receptor (CAR) - T cell therapy is a new class of cellular immunotherapies, which has made great achievements in the treatment of malignant tumors. Despite improvements in colorectal cancer (CRC) therapy, treatment of many patients fails because of metastasis and recurrence. The human epidermal growth factor receptor 2 (HER2) is a substantiated target for CAR-T therapy, and has been reported recently to be over-expressed in CRC, which may provide a potential therapeutic target for CRC treatment. Herein, HER2 was a promising target of metastatic colorectal cancer (mCRC) in CAR-T therapy as assessed by flow cytometry and tissue microarray (TMA) with 9-year survival follow-up data. Furthermore, HER2-specific CAR-T cells exhibited strong cytotoxicity and cytokine-secreting ability against CRC cells in vitro. Moreover, through the tumor-bearing model of the NOD-Prkdcem26cd52Il2rgem26Cd22/Nju (NCG) mice, HER2 CAR-T cells showed signs of effectively preventing CRC progression in three different xenograft models. Notably, HER2 CAR-T cells displayed greater aggressiveness in HER2+ CRC in the patient-derived tumor xenograft (PDX) models and had potent immunotherapeutic capacity for mCRC in the metastatic xenograft mouse models. In conclusion, our studies provide scientific evidence that HER2 CAR-T cells represent an emerging immunotherapy for the treatment of mCRC.
format	article
author	Jie Xu Qingtao Meng Hao Sun Xinwei Zhang Jun Yun Bin Li Shenshen Wu Xiaobo Li Hongbao Yang Haitao Zhu Michael Aschner Michela Relucenti Giuseppe Familiari Rui Chen
author_facet	Jie Xu Qingtao Meng Hao Sun Xinwei Zhang Jun Yun Bin Li Shenshen Wu Xiaobo Li Hongbao Yang Haitao Zhu Michael Aschner Michela Relucenti Giuseppe Familiari Rui Chen
author_sort	Jie Xu
title	HER2-specific chimeric antigen receptor-T cells for targeted therapy of metastatic colorectal cancer
title_short	HER2-specific chimeric antigen receptor-T cells for targeted therapy of metastatic colorectal cancer
title_full	HER2-specific chimeric antigen receptor-T cells for targeted therapy of metastatic colorectal cancer
title_fullStr	HER2-specific chimeric antigen receptor-T cells for targeted therapy of metastatic colorectal cancer
title_full_unstemmed	HER2-specific chimeric antigen receptor-T cells for targeted therapy of metastatic colorectal cancer
title_sort	her2-specific chimeric antigen receptor-t cells for targeted therapy of metastatic colorectal cancer
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/a951c8fcb43d4002b7844f3a23348587
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HER2-specific chimeric antigen receptor-T cells for targeted therapy of metastatic colorectal cancer

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