PMID- 17495947
OWN - NLM
STAT- MEDLINE
DCOM- 20071108
LR  - 20121115
IS  - 0969-7128 (Print)
IS  - 0969-7128 (Linking)
VI  - 14
IP  - 15
DP  - 2007 Aug
TI  - Synergistic antileukemia effect of combinational gene therapy using murine 
      beta-defensin 2 and IL-18 in L1210 murine leukemia model.
PG  - 1181-7
AB  - Murine beta-defensin 2 (MBD2) is not only chemotactic for immature dendritic 
      cells but also activates them by Toll-like receptor 4. We have previously 
      demonstrated that vaccine with MBD2 elicited potent antileukemia responses in the 
      L1210 murine model. Interleukin-18 (IL-18) is an essential cytokine for the 
      generation of Th1 response and natural killer cells and cytotoxic T lymphocytes 
      (CTL) activation. As MBD2 and IL-18 appear to function on different components 
      required by an effective antitumor immune response including both innate and 
      adaptive immunity, we investigated whether combinatorial delivery of MBD2 and 
      IL-18 transduced L1210 cells could elicit synergistic antileukemia effects. 
      First, we constructed a single plasmid vector carrying both pro-IL-18 and 
      IL-1beta converting enzyme (ICE) genes, and found that transfection of this 
      vector into L1210 cells resulted in efficient secretion of bioactive IL-18. 
      Combinatorial delivery of MBD2 and pro-IL-18-ICE modified L1210 cells conferred a 
      superior inhibition of leukemogenicity over either L1210-MBD2 or 
      L1210-pro-IL-18-ICE alone; moreover, the survived mice developed long-lasting 
      protective immunity as determined by rechallenge experiments. This combined 
      vaccine also elicited the most marked therapeutic effect, CTL activity and 
      interferon-gamma production. These results suggest that the combination of MBD2 
      and IL-18 induces more effective antileukemia activity and provides a promising 
      strategy for cancer therapy.
FAU - Xu, B
AU  - Xu B
AD  - State Key Laboratory for Experimental Hematology, Institute of Hematology, 
      Chinese Academy of Medical Sciences, Peking Union Medical College, Tianjin, 
      China.
FAU - Dong, C-Y
AU  - Dong CY
FAU - Zhang, F
AU  - Zhang F
FAU - Lin, Y-M
AU  - Lin YM
FAU - Wu, K-F
AU  - Wu KF
FAU - Ma, X-T
AU  - Ma XT
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070510
PL  - England
TA  - Gene Ther
JT  - Gene therapy
JID - 9421525
RN  - 0 (Cancer Vaccines)
RN  - 0 (DEFB4A protein, human)
RN  - 0 (Interleukin-18)
RN  - 0 (Interleukin-1beta)
RN  - 0 (beta-Defensins)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Animals
MH  - Biological Assay/methods
MH  - Cancer Vaccines/genetics/*therapeutic use
MH  - Cell Line
MH  - Gene Expression
MH  - Genetic Therapy/*methods
MH  - Genetic Vectors/*administration & dosage/genetics
MH  - Interferon-gamma/immunology
MH  - Interleukin-18/*genetics
MH  - Interleukin-1beta/metabolism
MH  - Killer Cells, Natural/immunology
MH  - Leukemia, Lymphoid/immunology/*therapy
MH  - Lymphocyte Activation
MH  - Mice
MH  - Models, Animal
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - T-Lymphocytes, Cytotoxic/immunology
MH  - Transfection/methods
MH  - Transgenes
MH  - beta-Defensins/*genetics
EDAT- 2007/05/15 09:00
MHDA- 2007/11/09 09:00
CRDT- 2007/05/15 09:00
PHST- 2007/05/15 09:00 [pubmed]
PHST- 2007/11/09 09:00 [medline]
PHST- 2007/05/15 09:00 [entrez]
AID - 3302966 [pii]
AID - 10.1038/sj.gt.3302966 [doi]
PST - ppublish
SO  - Gene Ther. 2007 Aug;14(15):1181-7. doi: 10.1038/sj.gt.3302966. Epub 2007 May 10.