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Antitumor activity of EGFR-specific CAR T cells against non-small-cell lung cancer cells in vitro and in mice

Effective control of non-small-cell lung cancer (NSCLC) remains clinically challenging, especially during advanced stages of the disease. This study developed an adoptive T-cell treatment through expression of a chimeric antigen receptor (CAR) to target human epidermal growth factor receptor (EGFR)...

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Autores principales: Li, He, Huang, Yao, Jiang, Du-Qing, Cui, Lian-Zhen, He, Zhou, Wang, Chao, Zhang, Zhi-Wei, Zhu, Hai-Li, Ding, Yong-Mei, Li, Lin-Fang, Li, Qiang, Jin, Hua-Jun, Qian, Qi-Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5833445/
https://www.ncbi.nlm.nih.gov/pubmed/29415996
http://dx.doi.org/10.1038/s41419-017-0238-6
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author Li, He
Huang, Yao
Jiang, Du-Qing
Cui, Lian-Zhen
He, Zhou
Wang, Chao
Zhang, Zhi-Wei
Zhu, Hai-Li
Ding, Yong-Mei
Li, Lin-Fang
Li, Qiang
Jin, Hua-Jun
Qian, Qi-Jun
author_facet Li, He
Huang, Yao
Jiang, Du-Qing
Cui, Lian-Zhen
He, Zhou
Wang, Chao
Zhang, Zhi-Wei
Zhu, Hai-Li
Ding, Yong-Mei
Li, Lin-Fang
Li, Qiang
Jin, Hua-Jun
Qian, Qi-Jun
author_sort Li, He
collection PubMed
description Effective control of non-small-cell lung cancer (NSCLC) remains clinically challenging, especially during advanced stages of the disease. This study developed an adoptive T-cell treatment through expression of a chimeric antigen receptor (CAR) to target human epidermal growth factor receptor (EGFR) in NSCLC. We optimized the non-viral piggyBac transposon system to engineer human T cells for the expression of EGFR-CAR, consisting of EGFR scFv, transmembrane domain, and intracellular 4-1BB-CD3ζ signaling domains. The modified CAR T cells exhibited expansion capability and anticancer efficacy in a time- and antigen-dependent manner in vitro as well as regression of EGFR-positive human lung cancer xenografts in vivo. EGFR-CAR T therapy is a promising strategy to improve the efficacy and potency of the adoptive immunotherapy in NSCLC. Moreover, EGFR-CAR T therapy could become a clinical application for NSCLC patients in the future.
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spelling pubmed-58334452018-03-05 Antitumor activity of EGFR-specific CAR T cells against non-small-cell lung cancer cells in vitro and in mice Li, He Huang, Yao Jiang, Du-Qing Cui, Lian-Zhen He, Zhou Wang, Chao Zhang, Zhi-Wei Zhu, Hai-Li Ding, Yong-Mei Li, Lin-Fang Li, Qiang Jin, Hua-Jun Qian, Qi-Jun Cell Death Dis Article Effective control of non-small-cell lung cancer (NSCLC) remains clinically challenging, especially during advanced stages of the disease. This study developed an adoptive T-cell treatment through expression of a chimeric antigen receptor (CAR) to target human epidermal growth factor receptor (EGFR) in NSCLC. We optimized the non-viral piggyBac transposon system to engineer human T cells for the expression of EGFR-CAR, consisting of EGFR scFv, transmembrane domain, and intracellular 4-1BB-CD3ζ signaling domains. The modified CAR T cells exhibited expansion capability and anticancer efficacy in a time- and antigen-dependent manner in vitro as well as regression of EGFR-positive human lung cancer xenografts in vivo. EGFR-CAR T therapy is a promising strategy to improve the efficacy and potency of the adoptive immunotherapy in NSCLC. Moreover, EGFR-CAR T therapy could become a clinical application for NSCLC patients in the future. Nature Publishing Group UK 2018-02-07 /pmc/articles/PMC5833445/ /pubmed/29415996 http://dx.doi.org/10.1038/s41419-017-0238-6 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Li, He
Huang, Yao
Jiang, Du-Qing
Cui, Lian-Zhen
He, Zhou
Wang, Chao
Zhang, Zhi-Wei
Zhu, Hai-Li
Ding, Yong-Mei
Li, Lin-Fang
Li, Qiang
Jin, Hua-Jun
Qian, Qi-Jun
Antitumor activity of EGFR-specific CAR T cells against non-small-cell lung cancer cells in vitro and in mice
title Antitumor activity of EGFR-specific CAR T cells against non-small-cell lung cancer cells in vitro and in mice
title_full Antitumor activity of EGFR-specific CAR T cells against non-small-cell lung cancer cells in vitro and in mice
title_fullStr Antitumor activity of EGFR-specific CAR T cells against non-small-cell lung cancer cells in vitro and in mice
title_full_unstemmed Antitumor activity of EGFR-specific CAR T cells against non-small-cell lung cancer cells in vitro and in mice
title_short Antitumor activity of EGFR-specific CAR T cells against non-small-cell lung cancer cells in vitro and in mice
title_sort antitumor activity of egfr-specific car t cells against non-small-cell lung cancer cells in vitro and in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5833445/
https://www.ncbi.nlm.nih.gov/pubmed/29415996
http://dx.doi.org/10.1038/s41419-017-0238-6
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