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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)...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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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. |
format | Online Article Text |
id | pubmed-5833445 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
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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