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B7-H3 chimeric antigen receptor-modified T cell shows potential for targeted treatment of acute myeloid leukaemia

BACKGROUND AND AIMS: Chimeric antigen receptor (CAR)-T cell therapy is a novel type of immunotherapy. However, the use of CAR-T cells to treat acute myeloid leukaemia (AML) has limitations. B7-H3 is expressed in several malignancies, including some types of AML cells. However, its expression in norm...

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Autores principales: Fan, Shuangshuang, Wang, Tian, You, Fengtao, Zhang, Tingting, Li, Yafen, Ji, Cheng, Han, Zhichao, Sheng, Binjie, Zhai, Xiaochen, An, Gangli, Meng, Huimin, Yang, Lin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10026503/
https://www.ncbi.nlm.nih.gov/pubmed/36941687
http://dx.doi.org/10.1186/s40001-023-01049-y
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author Fan, Shuangshuang
Wang, Tian
You, Fengtao
Zhang, Tingting
Li, Yafen
Ji, Cheng
Han, Zhichao
Sheng, Binjie
Zhai, Xiaochen
An, Gangli
Meng, Huimin
Yang, Lin
author_facet Fan, Shuangshuang
Wang, Tian
You, Fengtao
Zhang, Tingting
Li, Yafen
Ji, Cheng
Han, Zhichao
Sheng, Binjie
Zhai, Xiaochen
An, Gangli
Meng, Huimin
Yang, Lin
author_sort Fan, Shuangshuang
collection PubMed
description BACKGROUND AND AIMS: Chimeric antigen receptor (CAR)-T cell therapy is a novel type of immunotherapy. However, the use of CAR-T cells to treat acute myeloid leukaemia (AML) has limitations. B7-H3 is expressed in several malignancies, including some types of AML cells. However, its expression in normal tissues is low. Therefore, B7-H3 is ideal for targeted AML therapy. MATERIALS AND METHODS: First, we constructed B7-H3 CAR that can target B7-H3, and then constructed B7-H3-CAR-T cells in vitro, which were co-incubated with six AML cell lines expressing different levels of B7-H3, respectively. The toxicity and cytokines were detected by flow cytometry. In vivo, AML model was established in B-NSG mice to study the toxicity of B7-H3-CAR T on AML cells. RESULTS: In vitro functional tests showed that B7-H3-CAR-T cells were cytotoxic to B7-H3-positive AML tumor cells and had good scavenging effect on B7-H3-expressing AML cell lines, and the cytokine results were consistent. In vivo, B7-H3-CAR-T cells significantly inhibited tumor cell growth in a mouse model of AML, prolonging mouse survival compared with controls. CONCLUSION: B7-H3-CAR-T cells may serve as a novel therapeutic method for the targeted treatment of AML. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40001-023-01049-y.
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spelling pubmed-100265032023-03-21 B7-H3 chimeric antigen receptor-modified T cell shows potential for targeted treatment of acute myeloid leukaemia Fan, Shuangshuang Wang, Tian You, Fengtao Zhang, Tingting Li, Yafen Ji, Cheng Han, Zhichao Sheng, Binjie Zhai, Xiaochen An, Gangli Meng, Huimin Yang, Lin Eur J Med Res Research BACKGROUND AND AIMS: Chimeric antigen receptor (CAR)-T cell therapy is a novel type of immunotherapy. However, the use of CAR-T cells to treat acute myeloid leukaemia (AML) has limitations. B7-H3 is expressed in several malignancies, including some types of AML cells. However, its expression in normal tissues is low. Therefore, B7-H3 is ideal for targeted AML therapy. MATERIALS AND METHODS: First, we constructed B7-H3 CAR that can target B7-H3, and then constructed B7-H3-CAR-T cells in vitro, which were co-incubated with six AML cell lines expressing different levels of B7-H3, respectively. The toxicity and cytokines were detected by flow cytometry. In vivo, AML model was established in B-NSG mice to study the toxicity of B7-H3-CAR T on AML cells. RESULTS: In vitro functional tests showed that B7-H3-CAR-T cells were cytotoxic to B7-H3-positive AML tumor cells and had good scavenging effect on B7-H3-expressing AML cell lines, and the cytokine results were consistent. In vivo, B7-H3-CAR-T cells significantly inhibited tumor cell growth in a mouse model of AML, prolonging mouse survival compared with controls. CONCLUSION: B7-H3-CAR-T cells may serve as a novel therapeutic method for the targeted treatment of AML. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40001-023-01049-y. BioMed Central 2023-03-20 /pmc/articles/PMC10026503/ /pubmed/36941687 http://dx.doi.org/10.1186/s40001-023-01049-y Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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
Fan, Shuangshuang
Wang, Tian
You, Fengtao
Zhang, Tingting
Li, Yafen
Ji, Cheng
Han, Zhichao
Sheng, Binjie
Zhai, Xiaochen
An, Gangli
Meng, Huimin
Yang, Lin
B7-H3 chimeric antigen receptor-modified T cell shows potential for targeted treatment of acute myeloid leukaemia
title B7-H3 chimeric antigen receptor-modified T cell shows potential for targeted treatment of acute myeloid leukaemia
title_full B7-H3 chimeric antigen receptor-modified T cell shows potential for targeted treatment of acute myeloid leukaemia
title_fullStr B7-H3 chimeric antigen receptor-modified T cell shows potential for targeted treatment of acute myeloid leukaemia
title_full_unstemmed B7-H3 chimeric antigen receptor-modified T cell shows potential for targeted treatment of acute myeloid leukaemia
title_short B7-H3 chimeric antigen receptor-modified T cell shows potential for targeted treatment of acute myeloid leukaemia
title_sort b7-h3 chimeric antigen receptor-modified t cell shows potential for targeted treatment of acute myeloid leukaemia
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10026503/
https://www.ncbi.nlm.nih.gov/pubmed/36941687
http://dx.doi.org/10.1186/s40001-023-01049-y
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