PMID- 18672528
OWN - NLM
STAT- MEDLINE
DCOM- 20080912
LR  - 20101118
IS  - 1359-6535 (Print)
IS  - 1359-6535 (Linking)
VI  - 13
IP  - 4
DP  - 2008
TI  - Comparison of DNA- and mRNA-transfected mouse dendritic cells as potential 
      vaccines against the human papillomavirus type 16 associated oncoprotein E7.
PG  - 495-509
AB  - BACKGROUND: Dendritic cells (DCs) mediate the generation of strong cytotoxic 
      T-lymphocyte (CTL) responses by functioning in antigen presentation and exerting 
      adjuvant properties. We compared several activation markers and parameters of 
      biological activity of DNA- and mRNA-transfected DCs in vitro and in vivo. 
      METHODS: CpG-matured, bone marrow derived C57BL/6 mouse DCs were electroporated 
      either with enhanced green fluorescence protein (EGFP) or human papillomavirus 
      type 16 (HPV16) E7 expression plasmids or in vitro transcribed mRNAs encoding for 
      the codon-optimized E7 or a shuffled version thereof. Activation marker 
      expression and antigen presentation was analysed by fluorescence-activated cell 
      sorting. The migratory behaviour of transfected DCs were investigated by in vitro 
      chemotaxis experiments and cytokine expression by ELISA. CTL-priming capacity of 
      transfected DCs were determined by vaccination of mice. RESULTS: mRNA 
      transfection produced a two- to fourfold increase of the activation markers CD40, 
      CD80, CD86 and MHC I and MHC II molecules. Predominately antigen-expressing DCs 
      migrated after mRNA transfection. Furthermore, mRNA-transfected DCs were capable 
      of inducing a chemokine gradient. After maturation, electroporation and 
      activation with soluble CD40 ligand and interferon-y, DCs displayed a T-helper 
      cell type 2 cytokine expression pattern. Nevertheless, E7-transfected DCs were 
      able to prime E7-specific CTL responses in vivo. The highest E7-specific CTL 
      frequencies were found in mice immunized with mRNA-transfected DCs. The in vitro 
      expanded CTLs exerted functional E7-specific cytotoxic activity. CONCLUSIONS: 
      Genetically modified DCs are suitable vehicles for the induction of E7-specific 
      CTL responses in mice and hence could help to eradicate HPV-associated lesions in 
      humans.
FAU - Dell, Kerstin
AU  - Dell K
AD  - German Cancer Research Center (DKFZ), Heidelberg, Germany.
FAU - Klein, Corinna
AU  - Klein C
FAU - Gissmann, Lutz
AU  - Gissmann L
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - England
TA  - Antivir Ther
JT  - Antiviral therapy
JID - 9815705
RN  - 0 (DNA, Viral)
RN  - 0 (Oncogene Proteins, Viral)
RN  - 0 (Papillomavirus E7 Proteins)
RN  - 0 (Papillomavirus Vaccines)
RN  - 0 (RNA, Messenger)
RN  - 0 (oncogene protein E7, Human papillomavirus type 16)
RN  - 147336-22-9 (Green Fluorescent Proteins)
SB  - IM
MH  - Animals
MH  - Antigen Presentation
MH  - Bone Marrow Cells/immunology
MH  - *DNA, Viral/genetics/immunology/metabolism
MH  - Dendritic Cells/*immunology/metabolism
MH  - Electroporation
MH  - Female
MH  - Green Fluorescent Proteins/genetics
MH  - Humans
MH  - Lymphocyte Activation/immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Oncogene Proteins, Viral/genetics/*immunology/metabolism
MH  - Papillomavirus E7 Proteins
MH  - Papillomavirus Vaccines/genetics/*immunology
MH  - Plasmids
MH  - *RNA, Messenger/genetics/immunology/metabolism
MH  - T-Lymphocytes, Cytotoxic/immunology
MH  - Transfection
EDAT- 2008/08/05 09:00
MHDA- 2008/09/16 09:00
CRDT- 2008/08/05 09:00
PHST- 2008/08/05 09:00 [pubmed]
PHST- 2008/09/16 09:00 [medline]
PHST- 2008/08/05 09:00 [entrez]
PST - ppublish
SO  - Antivir Ther. 2008;13(4):495-509.