PMID- 22581115
OWN - NLM
STAT- MEDLINE
DCOM- 20121019
LR  - 20181201
IS  - 1791-2423 (Electronic)
IS  - 1019-6439 (Linking)
VI  - 41
IP  - 2
DP  - 2012 Aug
TI  - An IL-12/Shh-C domain fusion protein-based IL-12 autocrine loop for sustained 
      natural killer cell activation.
PG  - 661-9
LID - 10.3892/ijo.2012.1466 [doi]
AB  - The dependency of activated natural killer (NK) cells on the continuous support 
      of exogenous interleukin (IL)-2 for their in vivo survival, tumor localization 
      and consequently, their antitumor effect, is a major obstacle for NK 
      cell-mediated tumor therapy. In the present study, a fusion gene between IL-12 
      and mouse sonic hedgehog C-terminal domain (Shh-C) was constructed. The fusion 
      protein was autocatalytically processed to form cholesterol-modified IL-12 
      molecules and an autocrine loop of IL-12 was established for the sustained 
      activation of NK cells. The transduced NK cells matured more rapidly in vitro 
      with the enhanced expression of granule-related proteins. NKIL-12/Shh-C cells 
      reached the same proliferation rate as NK cells transduced with enhanced green 
      fluorescent protein (EGFP)/Shh-C (NKEGFP/Shh-C) with <10-fold IL-2 
      supplementation, suggesting that the fusion protein reduced the dependency of NK 
      cells on IL-2. The amount of interferon‑gamma (IFN-gamma) in the supernatants of 
      NKIL-12/Shh-C cells 5 and 7 days after transduction was significantly higher than 
      that in the supernatants of NKIL-12 cells. Immunofluorescent staining of lung 
      tissues from B16-bearing mice which had received an intravenous injection of 
      lentivirus-transduced NK cells without exogenous IL-2 confirmed that donor 
      NK cells successfully infiltrated into the lung tissues. The survival time of the 
      mice which had received NKIL-12/Shh-C cells was significantly prolonged compared 
      to the mice which had received NKEGFP/Shh-C cells.
FAU - Zhu, Lining
AU  - Zhu L
AD  - Department of Biological Sciences, Clemson University, Clemson, SC 29634, USA.
FAU - Zhao, Zhihui
AU  - Zhao Z
FAU - Wei, Yanzhang
AU  - Wei Y
FAU - Marcotte, William Jr
AU  - Marcotte W Jr
FAU - Wagner, Thomas E
AU  - Wagner TE
FAU - Yu, Xianzhong
AU  - Yu X
LA  - eng
PT  - Journal Article
DEP - 20120508
PL  - Greece
TA  - Int J Oncol
JT  - International journal of oncology
JID - 9306042
RN  - 0 (Cytokines)
RN  - 0 (Hedgehog Proteins)
RN  - 0 (Interleukin-2)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Shh protein, mouse)
RN  - 187348-17-0 (Interleukin-12)
SB  - IM
MH  - Adoptive Transfer
MH  - Animals
MH  - *Autocrine Communication
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Cell Survival
MH  - Cytokines/blood/metabolism
MH  - Cytotoxicity Tests, Immunologic
MH  - Cytotoxicity, Immunologic
MH  - Female
MH  - Hedgehog Proteins/biosynthesis/*genetics
MH  - Humans
MH  - Immunotherapy
MH  - Interleukin-12/biosynthesis/*genetics
MH  - Interleukin-2/physiology
MH  - Killer Cells, Natural/immunology/*physiology/transplantation
MH  - Lung/pathology
MH  - *Lymphocyte Activation
MH  - Melanoma, Experimental/blood/*therapy
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neoplasm Transplantation
MH  - Protein Structure, Tertiary
MH  - Recombinant Fusion Proteins/biosynthesis/*genetics
MH  - Transduction, Genetic
EDAT- 2012/05/15 06:00
MHDA- 2012/10/20 06:00
CRDT- 2012/05/15 06:00
PHST- 2012/01/31 00:00 [received]
PHST- 2012/03/02 00:00 [accepted]
PHST- 2012/05/15 06:00 [entrez]
PHST- 2012/05/15 06:00 [pubmed]
PHST- 2012/10/20 06:00 [medline]
AID - 10.3892/ijo.2012.1466 [doi]
PST - ppublish
SO  - Int J Oncol. 2012 Aug;41(2):661-9. doi: 10.3892/ijo.2012.1466. Epub 2012 May 8.