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CAR-T cells targeting CD38 and LMP1 exhibit robust antitumour activity against NK/T cell lymphoma

BACKGROUND: Natural killer/T cell lymphoma (NKTCL) is an aggressive lymphoma with a poor prognosis. Chimeric antigen receptor-transduced T (CAR-T) cell therapy has become a promising immunotherapeutic strategy against haematologic malignancies. METHODS: In this study, four CAR-T cell lines (CD38-CAR...

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Autores principales: Li, Hongwen, Song, Wenting, Wu, Jiazhuo, Shi, Zhuangzhuang, Gao, Yuyang, Li, Jiwei, Han, Lijuan, Zhang, Jianxiang, Li, Zhaoming, Li, Yong, Zhang, Mingzhi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10470138/
https://www.ncbi.nlm.nih.gov/pubmed/37649020
http://dx.doi.org/10.1186/s12916-023-03040-0
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author Li, Hongwen
Song, Wenting
Wu, Jiazhuo
Shi, Zhuangzhuang
Gao, Yuyang
Li, Jiwei
Han, Lijuan
Zhang, Jianxiang
Li, Zhaoming
Li, Yong
Zhang, Mingzhi
author_facet Li, Hongwen
Song, Wenting
Wu, Jiazhuo
Shi, Zhuangzhuang
Gao, Yuyang
Li, Jiwei
Han, Lijuan
Zhang, Jianxiang
Li, Zhaoming
Li, Yong
Zhang, Mingzhi
author_sort Li, Hongwen
collection PubMed
description BACKGROUND: Natural killer/T cell lymphoma (NKTCL) is an aggressive lymphoma with a poor prognosis. Chimeric antigen receptor-transduced T (CAR-T) cell therapy has become a promising immunotherapeutic strategy against haematologic malignancies. METHODS: In this study, four CAR-T cell lines (CD38-CAR, LMP1-CAR, CD38-LMP1 tandem CAR 1 and CD38-LMP1 tandem CAR 2) were generated. The effect of CAR-T cells against NKTCL cells was evaluated both in vitro and in vivo. Expression of T cell activation markers and cytokines produced by CAR-T cells were detected by flow cytometry. RESULTS: The four CAR-T cell lines could effectively eliminate malignant NKTCL cells. They could be activated and produce inflammatory cytokines in a target-dependent manner. In vivo tests showed that the CAR-T cells exhibited significant antitumour effects in a xenotransplanted NKTCL mouse model. CONCLUSIONS: In summary, four CAR-T cell lines exhibited significant cytotoxicity against NKTCL cells both in vitro and in vivo. These results indicated the effective therapeutic promise of CD38 and LMP1 CAR-T cells in NKTCL. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12916-023-03040-0.
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spelling pubmed-104701382023-09-01 CAR-T cells targeting CD38 and LMP1 exhibit robust antitumour activity against NK/T cell lymphoma Li, Hongwen Song, Wenting Wu, Jiazhuo Shi, Zhuangzhuang Gao, Yuyang Li, Jiwei Han, Lijuan Zhang, Jianxiang Li, Zhaoming Li, Yong Zhang, Mingzhi BMC Med Research Article BACKGROUND: Natural killer/T cell lymphoma (NKTCL) is an aggressive lymphoma with a poor prognosis. Chimeric antigen receptor-transduced T (CAR-T) cell therapy has become a promising immunotherapeutic strategy against haematologic malignancies. METHODS: In this study, four CAR-T cell lines (CD38-CAR, LMP1-CAR, CD38-LMP1 tandem CAR 1 and CD38-LMP1 tandem CAR 2) were generated. The effect of CAR-T cells against NKTCL cells was evaluated both in vitro and in vivo. Expression of T cell activation markers and cytokines produced by CAR-T cells were detected by flow cytometry. RESULTS: The four CAR-T cell lines could effectively eliminate malignant NKTCL cells. They could be activated and produce inflammatory cytokines in a target-dependent manner. In vivo tests showed that the CAR-T cells exhibited significant antitumour effects in a xenotransplanted NKTCL mouse model. CONCLUSIONS: In summary, four CAR-T cell lines exhibited significant cytotoxicity against NKTCL cells both in vitro and in vivo. These results indicated the effective therapeutic promise of CD38 and LMP1 CAR-T cells in NKTCL. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12916-023-03040-0. BioMed Central 2023-08-30 /pmc/articles/PMC10470138/ /pubmed/37649020 http://dx.doi.org/10.1186/s12916-023-03040-0 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Li, Hongwen
Song, Wenting
Wu, Jiazhuo
Shi, Zhuangzhuang
Gao, Yuyang
Li, Jiwei
Han, Lijuan
Zhang, Jianxiang
Li, Zhaoming
Li, Yong
Zhang, Mingzhi
CAR-T cells targeting CD38 and LMP1 exhibit robust antitumour activity against NK/T cell lymphoma
title CAR-T cells targeting CD38 and LMP1 exhibit robust antitumour activity against NK/T cell lymphoma
title_full CAR-T cells targeting CD38 and LMP1 exhibit robust antitumour activity against NK/T cell lymphoma
title_fullStr CAR-T cells targeting CD38 and LMP1 exhibit robust antitumour activity against NK/T cell lymphoma
title_full_unstemmed CAR-T cells targeting CD38 and LMP1 exhibit robust antitumour activity against NK/T cell lymphoma
title_short CAR-T cells targeting CD38 and LMP1 exhibit robust antitumour activity against NK/T cell lymphoma
title_sort car-t cells targeting cd38 and lmp1 exhibit robust antitumour activity against nk/t cell lymphoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10470138/
https://www.ncbi.nlm.nih.gov/pubmed/37649020
http://dx.doi.org/10.1186/s12916-023-03040-0
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