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IL-21 Optimizes the CAR-T Cell Preparation Through Improving Lentivirus Mediated Transfection Efficiency of T Cells and Enhancing CAR-T Cell Cytotoxic Activities

Adoptive immunotherapy using CAR-T cells is a promising curative treatment strategy for hematological malignancies. Current manufacture of clinical-grade CAR-T cells based on lentiviral/retrovirus transfection of T cells followed by anti-CD3/CD28 activation supplemented with IL-2 has been associated...

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Autores principales: Du, Li, Nai, Yaru, Shen, Meiying, Li, Tingting, Huang, Jingjing, Han, Xiaojian, Wang, Wang, Pang, Da, Jin, Aishun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220804/
https://www.ncbi.nlm.nih.gov/pubmed/34179083
http://dx.doi.org/10.3389/fmolb.2021.675179
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author Du, Li
Nai, Yaru
Shen, Meiying
Li, Tingting
Huang, Jingjing
Han, Xiaojian
Wang, Wang
Pang, Da
Jin, Aishun
author_facet Du, Li
Nai, Yaru
Shen, Meiying
Li, Tingting
Huang, Jingjing
Han, Xiaojian
Wang, Wang
Pang, Da
Jin, Aishun
author_sort Du, Li
collection PubMed
description Adoptive immunotherapy using CAR-T cells is a promising curative treatment strategy for hematological malignancies. Current manufacture of clinical-grade CAR-T cells based on lentiviral/retrovirus transfection of T cells followed by anti-CD3/CD28 activation supplemented with IL-2 has been associated with low transfection efficiency and usually based on the use of terminally differentiated effector T cells. Thus, improving the quality and the quantity of CAR-T cells are essential for optimizing the CAR-T cell preparation. In our study, we focus on the role of IL-21 in the γ(c) cytokine conditions for CAR-T cell preparation. We found for the first time that the addition of IL-21 in the CAR-T preparation improved T cell transfection efficiency through the reduction of IFN-γ expression 24–48 h after T cell activation. We also confirmed that IL-21 enhanced the enrichment and expansion of less differentiated CAR-T cells. Finally, we validated that IL-21 improved the CAR-T cell cytotoxicity, which was related to increased secretion of effector cytokines. Together, these findings can be used to optimize the CAR-T cell preparation.
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spelling pubmed-82208042021-06-24 IL-21 Optimizes the CAR-T Cell Preparation Through Improving Lentivirus Mediated Transfection Efficiency of T Cells and Enhancing CAR-T Cell Cytotoxic Activities Du, Li Nai, Yaru Shen, Meiying Li, Tingting Huang, Jingjing Han, Xiaojian Wang, Wang Pang, Da Jin, Aishun Front Mol Biosci Molecular Biosciences Adoptive immunotherapy using CAR-T cells is a promising curative treatment strategy for hematological malignancies. Current manufacture of clinical-grade CAR-T cells based on lentiviral/retrovirus transfection of T cells followed by anti-CD3/CD28 activation supplemented with IL-2 has been associated with low transfection efficiency and usually based on the use of terminally differentiated effector T cells. Thus, improving the quality and the quantity of CAR-T cells are essential for optimizing the CAR-T cell preparation. In our study, we focus on the role of IL-21 in the γ(c) cytokine conditions for CAR-T cell preparation. We found for the first time that the addition of IL-21 in the CAR-T preparation improved T cell transfection efficiency through the reduction of IFN-γ expression 24–48 h after T cell activation. We also confirmed that IL-21 enhanced the enrichment and expansion of less differentiated CAR-T cells. Finally, we validated that IL-21 improved the CAR-T cell cytotoxicity, which was related to increased secretion of effector cytokines. Together, these findings can be used to optimize the CAR-T cell preparation. Frontiers Media S.A. 2021-06-04 /pmc/articles/PMC8220804/ /pubmed/34179083 http://dx.doi.org/10.3389/fmolb.2021.675179 Text en Copyright © 2021 Du, Nai, Shen, Li, Huang, Han, Wang, Pang and Jin. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Biosciences
Du, Li
Nai, Yaru
Shen, Meiying
Li, Tingting
Huang, Jingjing
Han, Xiaojian
Wang, Wang
Pang, Da
Jin, Aishun
IL-21 Optimizes the CAR-T Cell Preparation Through Improving Lentivirus Mediated Transfection Efficiency of T Cells and Enhancing CAR-T Cell Cytotoxic Activities
title IL-21 Optimizes the CAR-T Cell Preparation Through Improving Lentivirus Mediated Transfection Efficiency of T Cells and Enhancing CAR-T Cell Cytotoxic Activities
title_full IL-21 Optimizes the CAR-T Cell Preparation Through Improving Lentivirus Mediated Transfection Efficiency of T Cells and Enhancing CAR-T Cell Cytotoxic Activities
title_fullStr IL-21 Optimizes the CAR-T Cell Preparation Through Improving Lentivirus Mediated Transfection Efficiency of T Cells and Enhancing CAR-T Cell Cytotoxic Activities
title_full_unstemmed IL-21 Optimizes the CAR-T Cell Preparation Through Improving Lentivirus Mediated Transfection Efficiency of T Cells and Enhancing CAR-T Cell Cytotoxic Activities
title_short IL-21 Optimizes the CAR-T Cell Preparation Through Improving Lentivirus Mediated Transfection Efficiency of T Cells and Enhancing CAR-T Cell Cytotoxic Activities
title_sort il-21 optimizes the car-t cell preparation through improving lentivirus mediated transfection efficiency of t cells and enhancing car-t cell cytotoxic activities
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220804/
https://www.ncbi.nlm.nih.gov/pubmed/34179083
http://dx.doi.org/10.3389/fmolb.2021.675179
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