PMID- 17235318
OWN - NLM
STAT- MEDLINE
DCOM- 20070626
LR  - 20201222
IS  - 1525-0016 (Print)
IS  - 1525-0016 (Linking)
VI  - 15
IP  - 2
DP  - 2007 Feb
TI  - Dendritic cell function after gene transfer with adenovirus-calcium phosphate 
      co-precipitates.
PG  - 386-92
AB  - Dendritic cells (DCs) are essential for initiating and directing antigen-specific 
      T-cell responses. Genetic modification of DC is under study for cancer 
      immunotherapy, vaccine development, and antigen-targeted immunosuppression. 
      Adenovirus (Ad) type 5 (Ad5)-mediated gene transfer to mouse bone marrow DCs and 
      human monocyte-derived DCs is inefficient because neither express the cognate 
      high-affinity Ads receptor. We show that co-precipitating adenoviral vectors with 
      calcium phosphate (CaPi) increased gene expression (2000-fold) and transduction 
      efficiency (50-fold) in mouse DC, primarily owing to receptor-independent viral 
      uptake. Moreover, Ad5:CaPi-treated DCs were activated to express the maturation 
      surface molecules CD40 and CD86, and to secrete proinflammatory cytokines tumor 
      necrosis factor-alpha and interleukin 6. However, neither DC transduction nor 
      maturation was dependent on viral protein interactions with cell surface 
      integrin. Ad5:CaPi also transduced human DC more efficiently than Ad5 alone, 
      similar to a genetically modified vector (Ad5f35) targeted to the CD46 receptor. 
      As such, this approach combines the efficiency of adenoviral-mediated endosomal 
      escape and nuclear trafficking with the receptor independence of nonviral gene 
      delivery. Importantly, CaPi co-precipitation could be used to functionally modify 
      DC to activate and expand cytomegalovirus-specific memory cytotoxic T 
      lymphocytes. This study identifies a simple technique to improve the efficacy of 
      current Ad5 gene transfer, in support of clinical adoptive immunotherapy.
FAU - Seiler, Michael P
AU  - Seiler MP
AD  - Interdepartmental Program in Cell and Molecular Biology, Baylor College of 
      Medicine, Houston, Texas 77030, USA.
FAU - Gottschalk, Stephen
AU  - Gottschalk S
FAU - Cerullo, Vincenzo
AU  - Cerullo V
FAU - Ratnayake, Maheshika
AU  - Ratnayake M
FAU - Mane, Viraj P
AU  - Mane VP
FAU - Clarke, Christian
AU  - Clarke C
FAU - Palmer, Donna J
AU  - Palmer DJ
FAU - Ng, Philip
AU  - Ng P
FAU - Rooney, Cliona M
AU  - Rooney CM
FAU - Lee, Brendan
AU  - Lee B
LA  - eng
GR  - 5P30DK056338/DK/NIDDK NIH HHS/United States
GR  - DK56787/DK/NIDDK NIH HHS/United States
GR  - R01 DK56787/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Ther
JT  - Molecular therapy : the journal of the American Society of Gene Therapy
JID - 100890581
RN  - 0 (Calcium Phosphates)
RN  - 0 (Capsid Proteins)
RN  - 0 (Integrins)
RN  - 97Z1WI3NDX (calcium phosphate)
SB  - IM
MH  - Adenoviridae/*genetics
MH  - Animals
MH  - Bone Marrow Cells/cytology/metabolism
MH  - Calcium Phosphates/*pharmacology
MH  - Capsid Proteins/genetics/metabolism
MH  - Dendritic Cells/drug effects/*metabolism
MH  - Female
MH  - Flow Cytometry
MH  - Genetic Vectors/genetics
MH  - Humans
MH  - Integrins/metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Protein Binding
MH  - T-Lymphocytes/drug effects/metabolism
MH  - Transfection/*methods
EDAT- 2007/01/20 09:00
MHDA- 2007/06/27 09:00
CRDT- 2007/01/20 09:00
PHST- 2007/01/20 09:00 [pubmed]
PHST- 2007/06/27 09:00 [medline]
PHST- 2007/01/20 09:00 [entrez]
AID - S1525-0016(16)31293-X [pii]
AID - 10.1038/sj.mt.6300029 [doi]
PST - ppublish
SO  - Mol Ther. 2007 Feb;15(2):386-92. doi: 10.1038/sj.mt.6300029.