Title
Transpresentation of interleukin-15 by IL-15/IL-15Ra mRNA-engineered human dendritic cells boosts antitumoral natural killer cell activity Transpresentation of interleukin-15 by IL-15/IL-15Ra mRNA-engineered human dendritic cells boosts antitumoral natural killer cell activity
Author
Faculty/Department
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences. Veterinary Sciences
Faculty of Medicine and Health Sciences
Publication type
article
Publication
Albany, N.Y :Impact Journals ,
Subject
Biology
Human medicine
Source (journal)
Oncotarget. - Albany, N.Y, 2010, currens
Volume/pages
6(2015) :42 , p. 44123-44133
ISSN
1949-2553
ISI
000369908800008
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
In cancer immunotherapy, the use of dendritic cell (DC)-based vaccination strategies can improve overall survival, but until now durable clinical responses remain scarce. To date, DC vaccines are designed primarily to induce effective T-cell responses, ignoring the antitumor activity potential of natural killer (NK) cells. Aiming to further improve current DC vaccination outcome, we engineered monocyte-derived DC to produce interleukin (IL)-15 and/or IL-15 receptor alpha (IL-15Ra) using mRNA electroporation. The addition of IL-15Ra to the protocol, enabling IL-15 transpresentation to neighboring NK cells, resulted in significantly better NK-cell activation compared to IL-15 alone. Next to upregulation of NK-cell membrane activation markers, IL-15 transpresentation resulted in increased NK-cell secretion of IFN-gamma, granzyme B and perforin. Moreover, IL-15-transpresenting DC/NK cell cocultures from both healthy donors and acute myeloid leukemia (AML) patients in remission showed markedly enhanced cytotoxic activity against NK cell sensitive and resistant tumor cells. Blocking IL-15 transpresentation abrogated NK cell-mediated cytotoxicity against tumor cells, pointing to a pivotal role of IL-15 transpresentation by IL-15Ra to exert its NK cell-activating effects. In conclusion, we report an attractive approach to improve antitumoral NK-cell activity in DC-based vaccine strategies through the use of IL-15/IL-15Ra mRNA-engineered designer DC.
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Full text (open access)
https://repository.uantwerpen.be/docman/irua/b7f661/132262.pdf
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