TY  - JOUR
A1  - Tognarelli, Sara
A1  - Wirsching, Sebastian
A1  - Metzler, Ivana von
A1  - Rais, Bushra
A1  - Jacobs, Benedikt
A1  - Serve, Hubert
A1  - Bader, Peter
A1  - Ullrich, Evelyn
T1  - Enhancing the activation and releasing the brakes : a double hit strategy to improve NK cell cytotoxicity against multiple myeloma
T2  - Frontiers in immunology
N2  - Natural killer (NK) cells are innate lymphocytes with a strong antitumor ability. In tumor patients, such as multiple myeloma (MM) patients, an elevated number of NK cells after stem cell transplantation (SCT) has been reported to be correlated with a higher overall survival rate. With the aim of improving NK cell use for adoptive cell therapy, we also addressed the cytotoxicity of patient-derived, cytokine-stimulated NK cells against MM cells at specific time points: at diagnosis and before and after autologous stem cell transplantation. Remarkably, after cytokine stimulation, the patients' NK cells did not significantly differ from those of healthy donors. In a small cohort of MM patients, we were able to isolate autologous tumor cells, and we could demonstrate that IL-2/15 stimulated autologous NK cells were able to significantly improve their killing capacity of autologous tumor cells. With the aim to further improve the NK cell killing capacity against MM cells, we investigated the potential use of NK specific check point inhibitors with focus on NKG2A because this inhibitory NK cell receptor was upregulated following ex vivo cytokine stimulation and MM cells showed HLA-E expression that could even be increased by exposure to IFN-γ. Importantly, blocking of NKG2A resulted in a significant increase in the NK cell-mediated lysis of different MM target cells. Finally, these results let suggest that combining cytokine induced NK cell activation and the specific check point inhibition of the NKG2A-mediated pathways can be an effective strategy to optimize NK cell therapeutic approaches for treatment of multiple myeloma.
KW  - multiple myeloma
KW  - autologous stem cell transplantation
KW  - NK cells
KW  - adoptive cell therapy
KW  - NKG2A blocking
KW  - checkpoint inhibition
Y1  - 2018
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/49279
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-492794
SN  - 1664-3224
N1  - Copyright © 2018 Tognarelli, Wirsching, von Metzler, Rais, Jacobs, Serve, Bader and Ullrich. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
VL  - 9
IS  - Art. 2743
SP  - 1
EP  - 15
PB  - Frontiers Media
CY  - Lausanne
ER  -