PMID- 27422115
OWN - NLM
STAT- MEDLINE
DCOM- 20170918
LR  - 20240426
IS  - 1432-0851 (Electronic)
IS  - 0340-7004 (Print)
IS  - 0340-7004 (Linking)
VI  - 65
IP  - 9
DP  - 2016 Sep
TI  - Uptake of synthetic naked RNA by skin-resident dendritic cells via 
      macropinocytosis allows antigen expression and induction of T-cell responses in 
      mice.
PG  - 1075-83
LID - 10.1007/s00262-016-1869-7 [doi]
AB  - Intradermal administration of antigen-encoding RNA has entered clinical testing 
      for cancer vaccination. However, insight into the underlying mechanism of RNA 
      uptake, translation and antigen presentation is still limited. Utilizing 
      pharmacologically optimized naked RNA, the dose-response kinetics revealed a rise 
      in reporter signal with increasing RNA amounts and a prolonged RNA translation of 
      reporter protein up to 30 days after intradermal injection. Dendritic cells (DCs) 
      in the dermis were shown to engulf RNA, and the signal arising from the reporter 
      RNA was significantly diminished after DC depletion. Macropinocytosis was 
      relevant for intradermal RNA uptake and translation in vitro and in vivo. By 
      combining intradermal RNA vaccination and inhibition of macropinocytosis, we show 
      that effective priming of antigen-specific CD8(+) T-cells also relies on this 
      uptake mechanism. This report demonstrates that direct antigen translation by 
      dermal DCs after intradermal naked RNA vaccination is relevant for efficient 
      priming of antigen-specific T-cells.
FAU - Selmi, Abderraouf
AU  - Selmi A
AD  - TRON-Translational Oncology at the University Medical Center of Johannes 
      Gutenberg University gGmbH, Freiligrathstrasse 12, 55131, Mainz, Germany.
AD  - Research Center for Immunotherapy (FZI), University Medical Center of Johannes 
      Gutenberg University, Mainz, Germany.
FAU - Vascotto, Fulvia
AU  - Vascotto F
AD  - TRON-Translational Oncology at the University Medical Center of Johannes 
      Gutenberg University gGmbH, Freiligrathstrasse 12, 55131, Mainz, Germany.
FAU - Kautz-Neu, Kordula
AU  - Kautz-Neu K
AD  - Department of Dermatology, University Medical Center of Johannes Gutenberg 
      University, Mainz, Germany.
FAU - Tureci, Ozlem
AU  - Tureci O
AD  - Cluster for Individualized Immune Intervention (CI3), Mainz, Germany.
FAU - Sahin, Ugur
AU  - Sahin U
AD  - TRON-Translational Oncology at the University Medical Center of Johannes 
      Gutenberg University gGmbH, Freiligrathstrasse 12, 55131, Mainz, Germany.
AD  - Research Center for Immunotherapy (FZI), University Medical Center of Johannes 
      Gutenberg University, Mainz, Germany.
AD  - BioNTech RNA Pharmaceuticals GmbH, Mainz, Germany.
FAU - von Stebut, Esther
AU  - von Stebut E
AD  - Department of Dermatology, University Medical Center of Johannes Gutenberg 
      University, Mainz, Germany.
FAU - Diken, Mustafa
AU  - Diken M
AD  - TRON-Translational Oncology at the University Medical Center of Johannes 
      Gutenberg University gGmbH, Freiligrathstrasse 12, 55131, Mainz, Germany. 
      Mustafa.Diken@TrOn-Mainz.de.
AD  - BioNTech RNA Pharmaceuticals GmbH, Mainz, Germany. Mustafa.Diken@TrOn-Mainz.de.
FAU - Kreiter, Sebastian
AU  - Kreiter S
AD  - TRON-Translational Oncology at the University Medical Center of Johannes 
      Gutenberg University gGmbH, Freiligrathstrasse 12, 55131, Mainz, Germany. 
      Sebastian.Kreiter@TrOn-Mainz.de.
AD  - BioNTech RNA Pharmaceuticals GmbH, Mainz, Germany. 
      Sebastian.Kreiter@TrOn-Mainz.de.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160715
PL  - Germany
TA  - Cancer Immunol Immunother
JT  - Cancer immunology, immunotherapy : CII
JID - 8605732
RN  - 63231-63-0 (RNA)
SB  - IM
MH  - Animals
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Dendritic Cells/immunology/*metabolism
MH  - Female
MH  - Humans
MH  - Injections, Intradermal
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Pinocytosis
MH  - RNA/administration & dosage/*pharmacokinetics
PMC - PMC11028682
OTO - NOTNLM
OT  - Cancer immunotherapy
OT  - Dermal dendritic cell
OT  - Intradermal vaccination
OT  - Macropinocytosis
OT  - Naked RNA
OT  - RNA vaccine
COIS- Ugur Sahin is a stock owner and management board member of BioNTech AG (Mainz, 
      Germany). Mustafa Diken and Sebastian Kreiter are working as advisors for 
      BioNTech RNA Pharmaceuticals GmbH. All other authors have no potential conflict 
      of interest.
EDAT- 2016/07/17 06:00
MHDA- 2017/09/19 06:00
PMCR- 2016/07/15
CRDT- 2016/07/17 06:00
PHST- 2016/03/17 00:00 [received]
PHST- 2016/07/08 00:00 [accepted]
PHST- 2016/07/17 06:00 [entrez]
PHST- 2016/07/17 06:00 [pubmed]
PHST- 2017/09/19 06:00 [medline]
PHST- 2016/07/15 00:00 [pmc-release]
AID - 10.1007/s00262-016-1869-7 [pii]
AID - 1869 [pii]
AID - 10.1007/s00262-016-1869-7 [doi]
PST - ppublish
SO  - Cancer Immunol Immunother. 2016 Sep;65(9):1075-83. doi: 
      10.1007/s00262-016-1869-7. Epub 2016 Jul 15.