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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| Hauptverfasser: | , , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
3 February 2022
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| In: |
Biomedicines
Year: 2022, Jahrgang: 10, Heft: 2, Pages: 1-14 |
| ISSN: | 2227-9059 |
| DOI: | 10.3390/biomedicines10020373 |
| Online-Zugang: | 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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| Verfasserangaben: | 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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| 520 | |a 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. | ||
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