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Proteasome inhibition enhances the anti-leukemic efficacy of chimeric antigen receptor (CAR) expressing NK cells against acute myeloid leukemia

Relapsed and refractory acute myeloid leukemia (AML) carries a dismal prognosis. CAR T cells have shown limited efficacy in AML, partially due to dysfunctional autologous T cells and the extended time for generation of patient specific CAR T cells. Allogeneic NK cell therapy is a promising alternati...

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Main Authors: Sedloev, David (Author) , Chen, Qian (Author) , Unglaub, Julia Marie (Author) , Schanda, Nicola (Author) , Yao, Hao (Author) , Besiridou, Eleni (Author) , Neuber, Brigitte (Author) , Schmitt, Anita (Author) , Raffel, Simon (Author) , Liu, Yi (Author) , Janssen, Maike (Author) , Müller-Tidow, Carsten (Author) , Schmitt, Michael (Author) , Sauer, Tim (Author)
Format: Article (Journal)
Language:English
Published: 16 September 2024
In: Journal of hematology & oncology
Year: 2024, Volume: 17, Pages: 1-22
ISSN:1756-8722
DOI:10.1186/s13045-024-01604-y
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1186/s13045-024-01604-y
Verlag, kostenfrei, Volltext: https://jhoonline.biomedcentral.com/articles/10.1186/s13045-024-01604-y
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Author Notes:David Sedloev, Qian Chen, Julia M. Unglaub, Nicola Schanda, Yao Hao, Eleni Besiridou, Brigitte Neuber, Anita Schmitt, Simon Raffel, Yi Liu, Maike Janssen, Carsten Müller-Tidow, Michael Schmitt and Tim Sauer
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Summary:Relapsed and refractory acute myeloid leukemia (AML) carries a dismal prognosis. CAR T cells have shown limited efficacy in AML, partially due to dysfunctional autologous T cells and the extended time for generation of patient specific CAR T cells. Allogeneic NK cell therapy is a promising alternative, but strategies to enhance efficacy and persistence may be necessary. Proteasome inhibitors (PI) induce changes in the surface proteome which may render malignant cells more vulnerable to NK mediated cytotoxicity. Here, we investigated the potential benefit of combining PIs with CAR-expressing allogeneic NK cells against AML.
Item Description:Gesehen am 10.02.2025
Physical Description:Online Resource
ISSN:1756-8722
DOI:10.1186/s13045-024-01604-y

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