PMID- 20885448
OWN - NLM
STAT- MEDLINE
DCOM- 20110623
LR  - 20201226
IS  - 1476-5500 (Electronic)
IS  - 0929-1903 (Linking)
VI  - 18
IP  - 2
DP  - 2011 Feb
TI  - Gene therapy with interleukin-10 receptor and interleukin-12 induces a protective 
      interferon-gamma-dependent response against B16F10-Nex2 melanoma.
PG  - 110-22
LID - 10.1038/cgt.2010.58 [doi]
AB  - Antitumor immune responses are associated with proinflammatory cytokines, whereas 
      tumor-developing animals generally have increased the production of 
      immunosuppressive cytokines. Here, we show that splenocytes from C57Bl/6 mice 
      resistant to low doses of B16F10-Nex2 melanoma cells produced twofold or higher 
      interferon-gamma (IFN-gamma)/interleukin-10 (IL-10) ratios, whereas cells from 
      tumor-bearing animals produced predominantly IL-10. IL-10-knockout (IL-10KO) mice 
      were significantly more resistant to B16F10-Nex2 development, producing increased 
      amounts of IL-12 and IFN-gamma. To neutralize IL-10 in vivo, aiming at cancer 
      therapy, recombinant eukaryotic plasmid expressing the soluble extracellular 
      region of the murine IL-10 receptor alpha-chain was constructed (pcDNA3-sIL-10R). 
      Plasmid-treated melanoma-challenged animals showed extended survival time, the 
      protective response was IFN-gamma dependent and enhanced by co-immunization with a 
      plasmid expressing IL-12. Dendritic cells (DCs) from IL-10KO mice, primed with 
      B16F10-Nex2 antigens (TAg), secreted increased amounts of T-helper 1-type 
      cytokines and increased the expression of surface activation markers. Vaccination 
      of C57Bl/6 mice with TAg-activated IL-10KO DCs, as well as with TAg-primed DCs 
      from C57Bl/6 mice transfected with pcDNA3-sIL10R plasmid, significantly increased 
      animal survival. In conclusion, an IFN-gamma-dependent protective response was 
      induced against B16F10-Nex2 cells by neutralization of IL-10 with pcDNA3-sIL10R 
      plasmid. This effect was enhanced by association with IL-12 gene therapy (80% 
      protection), and could be mediated by TAg-primed DCs.
FAU - Marchi, L H L
AU  - Marchi LH
AD  - Experimental Oncology Unit, Department of Microbiology, Immunology and 
      Parasitology, Universidade Federal de Sao Paulo-Escola Paulista de Medicina, Sao 
      Paulo, Brazil.
FAU - Paschoalin, T
AU  - Paschoalin T
FAU - Travassos, L R
AU  - Travassos LR
FAU - Rodrigues, E G
AU  - Rodrigues EG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101001
PL  - England
TA  - Cancer Gene Ther
JT  - Cancer gene therapy
JID - 9432230
RN  - 0 (Receptors, Interleukin-10)
RN  - 187348-17-0 (Interleukin-12)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - Dendritic Cells/immunology
MH  - Genetic Therapy/*methods
MH  - Humans
MH  - Immunotherapy, Adoptive/*methods
MH  - Interferon-gamma/*immunology
MH  - Interleukin-12/biosynthesis/*genetics/immunology
MH  - Male
MH  - Melanoma, Experimental/genetics/immunology/*therapy
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Plasmids/genetics
MH  - Receptors, Interleukin-10/biosynthesis/*genetics/immunology
MH  - Transfection
EDAT- 2010/10/05 06:00
MHDA- 2011/06/24 06:00
CRDT- 2010/10/02 06:00
PHST- 2010/10/02 06:00 [entrez]
PHST- 2010/10/05 06:00 [pubmed]
PHST- 2011/06/24 06:00 [medline]
AID - cgt201058 [pii]
AID - 10.1038/cgt.2010.58 [doi]
PST - ppublish
SO  - Cancer Gene Ther. 2011 Feb;18(2):110-22. doi: 10.1038/cgt.2010.58. Epub 2010 Oct 
      1.