PMID- 11533211
OWN - NLM
STAT- MEDLINE
DCOM- 20011011
LR  - 20181113
IS  - 0022-538X (Print)
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Linking)
VI  - 75
IP  - 19
DP  - 2001 Oct
TI  - Adeno-associated virus type 2-mediated transduction of human monocyte-derived 
      dendritic cells: implications for ex vivo immunotherapy.
PG  - 9493-501
AB  - Dendritic cells (DCs) are pivotal antigen-presenting cells for regulating immune 
      responses. A major focus of contemporary vaccine research is the genetic 
      modification of DCs to express antigens or immunomodulatory molecules, utilizing 
      a variety of viral and nonviral vectors, to induce antigen-specific immune 
      responses that ameliorate disease states as diverse as malignancy, infection, 
      autoimmunity, and allergy. The present study has evaluated adeno-associated virus 
      (AAV) type 2 as a vector for ex vivo gene transfer to human peripheral blood 
      monocyte (MO)-derived DCs. AAV is a nonpathogenic parvovirus that infects a wide 
      variety of human cell lineages in vivo and in vitro, for long-term transgene 
      expression without requirements for cell proliferation. The presented data 
      demonstrate that recombinant AAV (rAAV) can efficiently transduce MOs as well as 
      DCs generated by MO culture with granulocyte-macrophage colony-stimulating factor 
      plus interleukin in vitro. rAAV transgene expression in MO-derived DCs could be 
      enhanced by etoposide, previously reported to enhance AAV gene expression. rAAV 
      transduction of freshly purified MO followed by 7 days of culture with cytokines 
      to generate DCs, and subsequent sorting for coexpression of DC markers CD1a and 
      CD40, showed robust transgene expression as well as evidence of nuclear 
      localization of the rAAV genome in the DC population. Phenotypic analyses using 
      multiple markers and functional assays of one-way allogeneic mixed leukocyte 
      reactions indicated that rAAV-transduced MO-derived DCs were as equivalent to 
      nontransduced DCs. These results support the utility of rAAV vectors for future 
      human DC vaccine studies.
FAU - Ponnazhagan, S
AU  - Ponnazhagan S
AD  - Department of Pathology, University of Alabama at Birmingham, 35294-0007, USA. 
      sponnazh@path.uab.edu
FAU - Mahendra, G
AU  - Mahendra G
FAU - Curiel, D T
AU  - Curiel DT
FAU - Shaw, D R
AU  - Shaw DR
LA  - eng
GR  - P50 CA083591/CA/NCI NIH HHS/United States
GR  - R01 CA086881/CA/NCI NIH HHS/United States
GR  - 5 P50-CA83591/CA/NCI NIH HHS/United States
GR  - R01 CA86881-01/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
SB  - IM
MH  - Antigen Presentation/genetics
MH  - Cell Differentiation/immunology
MH  - Dendritic Cells/*immunology/pathology
MH  - Dependovirus/*genetics
MH  - *Genetic Vectors
MH  - Humans
MH  - *Immunotherapy
MH  - Monocytes/immunology/pathology
MH  - Transfection
PMC - PMC114516
EDAT- 2001/09/05 10:00
MHDA- 2001/10/12 10:01
PMCR- 2001/10/01
CRDT- 2001/09/05 10:00
PHST- 2001/09/05 10:00 [pubmed]
PHST- 2001/10/12 10:01 [medline]
PHST- 2001/09/05 10:00 [entrez]
PHST- 2001/10/01 00:00 [pmc-release]
AID - 0845 [pii]
AID - 10.1128/JVI.75.19.9493-9501.2001 [doi]
PST - ppublish
SO  - J Virol. 2001 Oct;75(19):9493-501. doi: 10.1128/JVI.75.19.9493-9501.2001.