PMID- 19609245
OWN - NLM
STAT- MEDLINE
DCOM- 20091008
LR  - 20181201
IS  - 1537-4513 (Electronic)
IS  - 1524-9557 (Linking)
VI  - 32
IP  - 5
DP  - 2009 Jun
TI  - Generation of human dendritic cells that simultaneously secrete IL-12 and have 
      migratory capacity by adenoviral gene transfer of hCD40L in combination with 
      IFN-gamma.
PG  - 524-38
LID - 10.1097/CJI.0b013e3181a28422 [doi]
AB  - Dendritic cells (DCs) are professional antigen presenting cells and have key 
      functions in the initiation of immune responses. Hence, antigen-loaded DCs have 
      become important tools for active-specific immunotherapy. In addition to defining 
      strategies for antigen loading, effective T-cell activation by DCs will depend on 
      vaccination protocols that facilitate DC migration to secondary lymphoid tissues 
      and expression of costimulatory molecules and cytokines. Adenoviral gene transfer 
      has been successfully implemented for genetic antigen loading of DCs. In this 
      study, we exploit an adenoviral vector encoding human CD40 ligand (CD40L), 
      Ad5hCD40L, to establish DCs that feature both migration potential and prolonged 
      secretion of the key T-helper 1 cytokine interleukin-12p70 (IL-12p70). 
      Transduction of human monocyte-derived DCs with Ad5hCD40L resulted in efficient 
      CD40L expression, which was detected only intracellularly, and in secretion of 
      IL-12p70. Addition of recombinant interferon (IFN)-gamma shortly after DC 
      transduction substantially increased IL-12p70 secretion. Maturation of DCs was 
      achieved with a standard cytokine maturation cocktail (MC) containing 
      prostaglandin E2 which, however, abolished IL-12p70 secretion by 
      Ad5hCD40L-transduced cells in the absence of IFN-gamma. Only DCs treated with 
      Ad5hCD40L, MC, and IFN-gamma migrated efficiently towards CCL19 and continued to 
      secrete IL-12p70. Finally, DCs transduced with both Ad5hCD40L and an adenoviral 
      vector encoding the melanoma antigen MelanA/MART-1 and treated with MC and 
      IFN-gamma efficiently primed naive autologous CD8+ T cells into antigen-specific 
      cytotoxic T lymphocyte. This strategy to generate DCs that exert both migration 
      capacity and prolonged IL-12p70 secretion after intracellular CD40L expression 
      and IFN-gamma treatment has the potential to further improve current DC 
      vaccination protocols.
FAU - Knippertz, Ilka
AU  - Knippertz I
AD  - Department of Dermatology, University Hospital Erlangen, Erlangen, Germany.
FAU - Hesse, Andrea
AU  - Hesse A
FAU - Schunder, Tanja
AU  - Schunder T
FAU - Kampgen, Eckhart
AU  - Kampgen E
FAU - Brenner, Malcolm K
AU  - Brenner MK
FAU - Schuler, Gerold
AU  - Schuler G
FAU - Steinkasserer, Alexander
AU  - Steinkasserer A
FAU - Nettelbeck, Dirk M
AU  - Nettelbeck DM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunother
JT  - Journal of immunotherapy (Hagerstown, Md. : 1997)
JID - 9706083
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Cancer Vaccines)
RN  - 0 (Chemokine CCL19)
RN  - 0 (MART-1 Antigen)
RN  - 0 (MLANA protein, human)
RN  - 0 (Neoplasm Proteins)
RN  - 147205-72-9 (CD40 Ligand)
RN  - 187348-17-0 (Interleukin-12)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Adenoviridae/*genetics
MH  - Antigen Presentation
MH  - Antigens, Neoplasm/genetics
MH  - CD40 Ligand/*genetics/immunology/*metabolism
MH  - CD8-Positive T-Lymphocytes/immunology/*metabolism/pathology
MH  - Cancer Vaccines
MH  - Cell Differentiation
MH  - Cell Movement
MH  - Chemokine CCL19/immunology/metabolism
MH  - Cytotoxicity, Immunologic
MH  - Dendritic Cells/*immunology/*metabolism/pathology
MH  - Genetic Vectors
MH  - Humans
MH  - Interferon-gamma/metabolism
MH  - Interleukin-12/metabolism
MH  - Lymphocyte Activation
MH  - MART-1 Antigen
MH  - Neoplasm Proteins/genetics
MH  - Th1 Cells/immunology/*metabolism/pathology
MH  - Transduction, Genetic
EDAT- 2009/07/18 09:00
MHDA- 2009/10/09 06:00
CRDT- 2009/07/18 09:00
PHST- 2009/07/18 09:00 [entrez]
PHST- 2009/07/18 09:00 [pubmed]
PHST- 2009/10/09 06:00 [medline]
AID - 00002371-200906000-00011 [pii]
AID - 10.1097/CJI.0b013e3181a28422 [doi]
PST - ppublish
SO  - J Immunother. 2009 Jun;32(5):524-38. doi: 10.1097/CJI.0b013e3181a28422.