PMID- 34638566
OWN - NLM
STAT- MEDLINE
DCOM- 20211028
LR  - 20211028
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 22
IP  - 19
DP  - 2021 Sep 23
TI  - A Chimeric IL-15/IL-15Ralpha Molecule Expressed on NFkappaB-Activated Dendritic Cells 
      Supports Their Capability to Activate Natural Killer Cells.
LID - 10.3390/ijms221910227 [doi]
LID - 10227
AB  - Natural killer (NK) cells, members of the innate immune system, play an important 
      role in the rejection of HLA class I negative tumor cells. Hence, a therapeutic 
      vaccine, which can activate NK cells in addition to cells of the adaptive immune 
      system might induce a more comprehensive cellular response, which could lead to 
      increased tumor elimination. Dendritic cells (DCs) are capable of activating and 
      expanding NK cells, especially when the NFkappaB pathway is activated in the DCs 
      thereby leading to the secretion of the cytokine IL-12. Another prominent NK cell 
      activator is IL-15, which can be bound by the IL-15 receptor alpha-chain 
      (IL-15Ralpha) to be transpresented to the NK cells. However, monocyte-derived DCs do 
      neither secrete IL-15, nor express the IL-15Ralpha. Hence, we designed a chimeric 
      protein consisting of IL-15 and the IL-15Ralpha. Upon mRNA electroporation, the 
      fusion protein was detectable on the surface of the DCs, and increased the 
      potential of NFkappaB-activated, IL-12-producing DC to activate NK cells in an 
      autologous cell culture system with ex vivo-generated cells from healthy donors. 
      These data show that a chimeric IL-15/IL-15Ralpha molecule can be expressed by 
      monocyte-derived DCs, is trafficked to the cell surface, and is functional 
      regarding the activation of NK cells. These data represent an initial 
      proof-of-concept for an additional possibility of further improving cellular 
      DC-based immunotherapies of cancer.
FAU - Bosch, Naomi C
AU  - Bosch NC
AD  - Institute of Medical Immunology, Martin-Luther University Halle-Wittenberg, 06112 
      Halle (Saale), Germany.
AD  - Department of Dermatology, Universitatsklinikum Erlangen, Friedrich-Alexander 
      University Erlangen-Nurnberg, 91054 Erlangen, Germany.
AD  - Comprehensive Cancer Center Erlangen-EMN, NCT WERA, 91054 Erlangen, Germany.
FAU - Martin, Lena-Marie
AU  - Martin LM
AD  - Department of Dermatology, Universitatsklinikum Erlangen, Friedrich-Alexander 
      University Erlangen-Nurnberg, 91054 Erlangen, Germany.
FAU - Voskens, Caroline J
AU  - Voskens CJ
AD  - Department of Dermatology, Universitatsklinikum Erlangen, Friedrich-Alexander 
      University Erlangen-Nurnberg, 91054 Erlangen, Germany.
AD  - Comprehensive Cancer Center Erlangen-EMN, NCT WERA, 91054 Erlangen, Germany.
AD  - Deutsches Zentrum Immuntherapie (DZI), 91054 Erlangen, Germany.
FAU - Berking, Carola
AU  - Berking C
AUID- ORCID: 0000-0003-0229-8931
AD  - Department of Dermatology, Universitatsklinikum Erlangen, Friedrich-Alexander 
      University Erlangen-Nurnberg, 91054 Erlangen, Germany.
AD  - Comprehensive Cancer Center Erlangen-EMN, NCT WERA, 91054 Erlangen, Germany.
AD  - Deutsches Zentrum Immuntherapie (DZI), 91054 Erlangen, Germany.
FAU - Seliger, Barbara
AU  - Seliger B
AUID- ORCID: 0000-0002-5544-4958
AD  - Institute of Medical Immunology, Martin-Luther University Halle-Wittenberg, 06112 
      Halle (Saale), Germany.
AD  - Fraunhofer Institute for Cell Therapy and Immunology (IZI), 04103 Leipzig, 
      Germany.
FAU - Schuler, Gerold
AU  - Schuler G
AD  - Department of Dermatology, Universitatsklinikum Erlangen, Friedrich-Alexander 
      University Erlangen-Nurnberg, 91054 Erlangen, Germany.
FAU - Schaft, Niels
AU  - Schaft N
AUID- ORCID: 0000-0001-8236-9298
AD  - Department of Dermatology, Universitatsklinikum Erlangen, Friedrich-Alexander 
      University Erlangen-Nurnberg, 91054 Erlangen, Germany.
FAU - Dorrie, Jan
AU  - Dorrie J
AUID- ORCID: 0000-0002-3478-0741
AD  - Department of Dermatology, Universitatsklinikum Erlangen, Friedrich-Alexander 
      University Erlangen-Nurnberg, 91054 Erlangen, Germany.
LA  - eng
GR  - SFB643 (project C1)/Deutsche Forschungsgemeinschaft/
GR  - 34102524/Deutsche Krebshilfe/
PT  - Journal Article
DEP - 20210923
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (IL15 protein, human)
RN  - 0 (IL15RA protein, human)
RN  - 0 (Interleukin-15)
RN  - 0 (NF-kappa B)
RN  - 0 (Receptors, Interleukin-15)
RN  - 0 (Recombinant Fusion Proteins)
RN  - EC 2.7.11.10 (I-kappa B Kinase)
SB  - IM
MH  - Dendritic Cells/drug effects/*immunology
MH  - Electroporation
MH  - Humans
MH  - I-kappa B Kinase/biosynthesis/genetics
MH  - Immunotherapy
MH  - Interleukin-15/*biosynthesis/chemistry/genetics
MH  - Killer Cells, Natural/drug effects/*immunology
MH  - Leukocytes, Mononuclear
MH  - NF-kappa B/pharmacology
MH  - Primary Cell Culture
MH  - Receptors, Interleukin-15/*biosynthesis/chemistry/genetics
MH  - Recombinant Fusion Proteins/*biosynthesis/chemistry/genetics
PMC - PMC8508776
OTO - NOTNLM
OT  - IL-15
OT  - NF-kappaB
OT  - adoptive cellular immunotherapy
OT  - dendritic cell
OT  - natural killer cell
COIS- The authors declare the following potential conflict of interest: GS, NS, and JD 
      are named as inventors on a patent on caIKK-RNA-electroporated DCs 
      (WO/2012/055551), which is held by the Friedrich-Alexander-University 
      Erlangen-Nurnberg (FAU).
EDAT- 2021/10/14 06:00
MHDA- 2021/10/29 06:00
PMCR- 2021/09/23
CRDT- 2021/10/13 01:02
PHST- 2021/07/30 00:00 [received]
PHST- 2021/09/02 00:00 [revised]
PHST- 2021/09/18 00:00 [accepted]
PHST- 2021/10/13 01:02 [entrez]
PHST- 2021/10/14 06:00 [pubmed]
PHST- 2021/10/29 06:00 [medline]
PHST- 2021/09/23 00:00 [pmc-release]
AID - ijms221910227 [pii]
AID - ijms-22-10227 [pii]
AID - 10.3390/ijms221910227 [doi]
PST - epublish
SO  - Int J Mol Sci. 2021 Sep 23;22(19):10227. doi: 10.3390/ijms221910227.