PMID- 18084244
OWN - NLM
STAT- MEDLINE
DCOM- 20080219
LR  - 20211020
IS  - 1476-5500 (Electronic)
IS  - 0929-1903 (Print)
IS  - 0929-1903 (Linking)
VI  - 15
IP  - 2
DP  - 2008 Feb
TI  - Treatment of pulmonary metastatic tumors in mice using lentiviral 
      vector-engineered stem cells.
PG  - 73-84
AB  - Active cancer immunotherapy relies on functional tumor-specific effector T 
      lymphocytes for tumor elimination. Dendritic cells (DCs), as most potent 
      antigen-presenting cells, have been popularly employed in clinical and 
      experimental tumor treatments. We have previously demonstrated that lentiviral 
      vector-mediated transgene delivery to DC progenitors, including bone marrow cells 
      and hematopoietic stem cells, followed by transplantation supports systemic 
      generation of great numbers of tumor antigen-presenting DCs. These DCs 
      subsequently stimulate marked and systemic immune activation. Here, we examined 
      whether this level of immune activation is sufficient to overcome tumor-induced 
      tolerogenic environment for treating an established aggressive epithelial tumor. 
      We showed that a combination treatment of granulocyte macrophage-colony 
      stimulating factor and cytosine-phosphate-guanine-containing oligonucleotide 
      stimulated large numbers of tumor antigen-presenting DCs in situ from 
      transgene-modified stem cells. Moreover, these in situ generated and activated 
      DCs markedly stimulated activation of antigen-specific CD4 and CD8 T cells by 
      augmenting their numbers, as well as function, even in a tumor-bearing 
      tolerogenic environment. This leads to significant improvement in the therapeutic 
      efficacy of established pulmonary metastases. This study suggests that lentiviral 
      vector-modified stem cells as DC progenitors may be used as an effective 
      therapeutic regimen for treating metastatic epithelial tumors.
FAU - Zhang, X
AU  - Zhang X
AD  - Gene Therapy Program, Department of Medicine, Louisiana State University Health 
      Sciences Center, New Orleans, LA 70112, USA.
FAU - Zhao, P
AU  - Zhao P
FAU - Kennedy, C
AU  - Kennedy C
FAU - Chen, K
AU  - Chen K
FAU - Wiegand, J
AU  - Wiegand J
FAU - Washington, G
AU  - Washington G
FAU - Marrero, L
AU  - Marrero L
FAU - Cui, Y
AU  - Cui Y
LA  - eng
GR  - P20RR021970/RR/NCRR NIH HHS/United States
GR  - R01 CA112065-03/CA/NCI NIH HHS/United States
GR  - P20 RR021970/RR/NCRR NIH HHS/United States
GR  - R01 CA112065/CA/NCI NIH HHS/United States
GR  - CA112065/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20071214
PL  - England
TA  - Cancer Gene Ther
JT  - Cancer gene therapy
JID - 9432230
SB  - IM
MH  - Animals
MH  - Carcinoma, Renal Cell/secondary/therapy
MH  - Cell Line
MH  - Cell Line, Tumor
MH  - Dendritic Cells/metabolism/transplantation
MH  - Female
MH  - *Gene Transfer Techniques
MH  - *Genetic Therapy/methods
MH  - *Genetic Vectors
MH  - Humans
MH  - Immunotherapy, Adoptive
MH  - Lentivirus/*genetics
MH  - Lung Neoplasms/*secondary/*therapy
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Transgenic
MH  - *Stem Cell Transplantation
MH  - Stem Cells/*metabolism
PMC - PMC2258434
MID - NIHMS41035
EDAT- 2007/12/18 09:00
MHDA- 2008/02/20 09:00
PMCR- 2008/02/29
CRDT- 2007/12/18 09:00
PHST- 2007/12/18 09:00 [pubmed]
PHST- 2008/02/20 09:00 [medline]
PHST- 2007/12/18 09:00 [entrez]
PHST- 2008/02/29 00:00 [pmc-release]
AID - 7701108 [pii]
AID - 10.1038/sj.cgt.7701108 [doi]
PST - ppublish
SO  - Cancer Gene Ther. 2008 Feb;15(2):73-84. doi: 10.1038/sj.cgt.7701108. Epub 2007 
      Dec 14.