Improving the Clinical Application of Natural Killer Cells by Modulating Signals Signal from Target Cells

Journal article


Holubova, M., Leba, M., Gmucova, H., Caputo Galarce, V., Jindra, P. and Lysak, D. (2019). Improving the Clinical Application of Natural Killer Cells by Modulating Signals Signal from Target Cells. International Journal of Molecular Sciences. 20 (14), p. 3472. https://doi.org/10.3390/ijms20143472
AuthorsHolubova, M., Leba, M., Gmucova, H., Caputo Galarce, V., Jindra, P. and Lysak, D.
Abstract

Relapsed acute myeloid leukemia (AML) is a significant post-transplant complication lacking standard treatment and associated with a poor prognosis. Cellular therapy, which is already widely used as a treatment for several hematological malignancies, could be a potential treatment alternative. Natural killer (NK) cells play an important role in relapse control but can be inhibited by the leukemia cells highly positive for HLA class I. In order to restore NK cell activity after their ex vivo activation, NK cells can be combined with conditioning target cells. In this study, we tested NK cell activity against KG1a (AML cell line) with and without two types of pretreatment-Ara-C treatment that induced NKG2D ligands (increased activating signal) and/or blocking of HLA-KIR (killer-immunoglobulin-like receptors) interaction (decreased inhibitory signal). Both treatments improved NK cell killing activity. Compared with target cell killing of NK cells alone (38%), co-culture with Ara-C treated KG1a target cells increased the killing to 80%. Anti-HLA blocking antibody treatment increased the proportion of dead KG1a cells to 53%. Interestingly, the use of the combination treatment improved the killing potential to led to the death of 85% of KG1a cells. The combination of Ara-C and ex vivo activation of NK cells has the potential to be a feasible approach to treat relapsed AML after hematopoietic stem cell transplantation.

Keywords HLA-KIR; NK cells; NKG2D; ligands; relapsed AML
Year2019
JournalInternational Journal of Molecular Sciences
Journal citation20 (14), p. 3472
PublisherMDPI
ISSN1661-6596
Digital Object Identifier (DOI)https://doi.org/10.3390/ijms20143472
Publication dates
Online15 Jul 2019
Publication process dates
Accepted14 Jul 2019
Deposited17 Jun 2021
Publisher's version
License
File Access Level
Open
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