RNA silencing of GM-CSF in CAR-T cells reduces the secretion of multiple inflammatory cytokines

Chimeric antigen receptor T (CAR-T) cell therapy has become a research hotspot in the field of hematological malignancies. However, CAR-T cell therapy can lead to immunotherapy-associated side effects including cytokine release syndrome and neurotoxicity. Gene depletion of GM-CSF in CAR-T cells was...

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Autores principales: Shang, Siqi, Chen, Yunshuo, Yang, Xuejiao, Yang, Ying, Wang, Wenbo, Wang, Yueying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2023
Materias:
Research
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10050814/
https://www.ncbi.nlm.nih.gov/pubmed/36988829
http://dx.doi.org/10.1007/s10637-023-01344-9
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author Shang, Siqi
Chen, Yunshuo
Yang, Xuejiao
Yang, Ying
Wang, Wenbo
Wang, Yueying
author_facet Shang, Siqi
Chen, Yunshuo
Yang, Xuejiao
Yang, Ying
Wang, Wenbo
Wang, Yueying
author_sort Shang, Siqi
collection PubMed
description Chimeric antigen receptor T (CAR-T) cell therapy has become a research hotspot in the field of hematological malignancies. However, CAR-T cell therapy can lead to immunotherapy-associated side effects including cytokine release syndrome and neurotoxicity. Gene depletion of GM-CSF in CAR-T cells was found preventive against adverse effects, but additional transfections were required to produce CAR-T cells. In this study, we interrupted GM-CSF expression in CAR-T cells by inserting the GM-CSF shRNA-expression cassette in the CAR vector. Reduction of GM-CSF in CAR-T cells could decrease the level of several proinflammatory cytokines without hampering the killing capacity. The manufacture of GM-CSF knockdown CAR-T cells does not require complicated transfections, which makes it more practical and feasible for clinical application. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10637-023-01344-9.
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spelling pubmed-100508142023-03-29 RNA silencing of GM-CSF in CAR-T cells reduces the secretion of multiple inflammatory cytokines Shang, Siqi Chen, Yunshuo Yang, Xuejiao Yang, Ying Wang, Wenbo Wang, Yueying Invest New Drugs Research Chimeric antigen receptor T (CAR-T) cell therapy has become a research hotspot in the field of hematological malignancies. However, CAR-T cell therapy can lead to immunotherapy-associated side effects including cytokine release syndrome and neurotoxicity. Gene depletion of GM-CSF in CAR-T cells was found preventive against adverse effects, but additional transfections were required to produce CAR-T cells. In this study, we interrupted GM-CSF expression in CAR-T cells by inserting the GM-CSF shRNA-expression cassette in the CAR vector. Reduction of GM-CSF in CAR-T cells could decrease the level of several proinflammatory cytokines without hampering the killing capacity. The manufacture of GM-CSF knockdown CAR-T cells does not require complicated transfections, which makes it more practical and feasible for clinical application. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10637-023-01344-9. Springer US 2023-03-29 2023 /pmc/articles/PMC10050814/ /pubmed/36988829 http://dx.doi.org/10.1007/s10637-023-01344-9 Text en © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
spellingShingle Research
Shang, Siqi
Chen, Yunshuo
Yang, Xuejiao
Yang, Ying
Wang, Wenbo
Wang, Yueying
RNA silencing of GM-CSF in CAR-T cells reduces the secretion of multiple inflammatory cytokines
title RNA silencing of GM-CSF in CAR-T cells reduces the secretion of multiple inflammatory cytokines
title_full RNA silencing of GM-CSF in CAR-T cells reduces the secretion of multiple inflammatory cytokines
title_fullStr RNA silencing of GM-CSF in CAR-T cells reduces the secretion of multiple inflammatory cytokines
title_full_unstemmed RNA silencing of GM-CSF in CAR-T cells reduces the secretion of multiple inflammatory cytokines
title_short RNA silencing of GM-CSF in CAR-T cells reduces the secretion of multiple inflammatory cytokines
title_sort rna silencing of gm-csf in car-t cells reduces the secretion of multiple inflammatory cytokines
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10050814/
https://www.ncbi.nlm.nih.gov/pubmed/36988829
http://dx.doi.org/10.1007/s10637-023-01344-9
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