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HDAC inhibition for optimized cellular immunotherapy of NY-ESO-1-positive soft tissue sarcoma

Adoptive cell therapy with NY-ESO-1-specific T cells is a promising option for the treatment of soft tissue sarcoma (STS) but achieves only transient tumor control in the majority of cases. A strategy to optimize this cell therapeutic approach might be the modulation of the expression of the cancer-...

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Main Authors: Gong, Wenjie (Author) , Wang, Lei (Author) , Schubert, Maria-Luisa (Author) , Kleist, Christian (Author) , Neuber, Brigitte (Author) , Wang, Sanmei (Author) , Yang, Mingya (Author) , Hückelhoven-Krauss, Angela (Author) , Wu, Depei (Author) , Schmitt, Anita (Author) , Müller-Tidow, Carsten (Author) , Shiku, Hiroshi (Author) , Schmitt, Michael (Author) , Sellner, Leopold (Author)
Format: Article (Journal)
Language:English
Published: 3 February 2022
In: Biomedicines
Year: 2022, Volume: 10, Issue: 2, Pages: 1-14
ISSN:2227-9059
DOI:10.3390/biomedicines10020373
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3390/biomedicines10020373
Verlag, lizenzpflichtig, Volltext: https://www.mdpi.com/2227-9059/10/2/373
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Author Notes:Wenjie Gong, Lei Wang, Maria-Luisa Schubert, Christian Kleist, Brigitte Neuber, Sanmei Wang, Mingya Yang, Angela Hückelhoven-Krauss, Depei Wu, Anita Schmitt, Carsten Müller-Tidow, Hiroshi Shiku, Michael Schmitt and Leopold Sellner
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Summary:Adoptive cell therapy with NY-ESO-1-specific T cells is a promising option for the treatment of soft tissue sarcoma (STS) but achieves only transient tumor control in the majority of cases. A strategy to optimize this cell therapeutic approach might be the modulation of the expression of the cancer-testis antigen NY-ESO-1 using histone deacetylase inhibitors (HDACis). In this study, the ex vivo effect of combining NY-ESO-1-specific T cells with the clinically approved pan HDACis panobinostat or vorionstat was investigated. Our data demonstrated that STS cells were sensitive to HDACis. Administration of HDACi prior to NY-ESO-1-specific T cells exerted enhanced lysis against the NY-ESO-1+ STS cell line SW982. This correlated with an increase in the NY-ESO-1 and HLA-ABC expression of SW982 cells, as well as increased CD25 expression on NY-ESO-1-specific T cells. Furthermore, the immune reactivity of NY-ESO-1-specific CD8+ T cells in terms of cytokine release was enhanced by HDACis. In summary, pretreatment with HDACis represents a potential means of enhancing the cytotoxic efficacy of NY-ESO-1-specific T cells against NY-ESO-1-positive STS.
Item Description:Gesehen am 12.06.2022
Physical Description:Online Resource
ISSN:2227-9059
DOI:10.3390/biomedicines10020373

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