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HDAC Inhibition for Optimized Cellular Immunotherapy of NY-ESO-1-Positive Soft Tissue Sarcoma

Authors :
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
Leopold Sellner
Source :
Biomedicines, Vol 10, Iss 2, p 373 (2022)
Publication Year :
2022
Publisher :
MDPI AG, 2022.

Abstract

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.

Details

Language :
English
ISSN :
10020373 and 22279059
Volume :
10
Issue :
2
Database :
Directory of Open Access Journals
Journal :
Biomedicines
Publication Type :
Academic Journal
Accession number :
edsdoj.6650dcceca714b109d1d13c489035f8e
Document Type :
article
Full Text :
https://doi.org/10.3390/biomedicines10020373