PMID- 15076136
OWN - NLM
STAT- MEDLINE
DCOM- 20041221
LR  - 20231213
IS  - 1524-9557 (Print)
IS  - 1524-9557 (Linking)
VI  - 27
IP  - 3
DP  - 2004 May-Jun
TI  - Human dendritic cell maturation by adenovirus transduction enhances tumor 
      antigen-specific T-cell responses.
PG  - 191-200
AB  - Dendritic cells (DCs) have been shown to require a degree of maturation to 
      stimulate antigen-specific, type 1 cytotoxic T lymphocytes in numerous murine 
      models. Limited data in humans suggest that immature DCs (DC) can induce 
      tolerance, yet a variety of nonmatured DC used clinically have induced 
      antigen-specific type 1 T cells in vivo to various tumor-associated antigens. Use 
      of adenovirus to engineer DCs is an efficient method for delivery of entire genes 
      to DC, but the data on the biologic effects of viral transduction are 
      contradictory. The authors demonstrate that DCs transduced with adenovirus (AdV) 
      clearly become more mature by the phenotypic criterion of upregulation of CD83 
      and downregulation of CD14. Transduced DCs also decrease production of IL-10, and 
      a subset of transduced DCs produce increased levels of IL-12 p70. This level of 
      maturation is superior to that achieved by treatment of these cells with tumor 
      necrosis factor-alpha or interferon-alpha but less pronounced than with CD40L 
      trimer or CD40L + interferon-gamma. Maturation by AdV transduction alone leads to 
      efficient stimulation of antigen-specific T cells from both healthy donors and 
      patients with advanced cancer using two defined human tumor-associated antigens, 
      MART-1 and AFP. Given the pivotal role of DCs in immune activation, it is 
      important to understand the direct biologic effects of AdV on DCs, as well as the 
      impact these biologic changes have on the stimulation of antigen-specific T 
      cells. This study has important implications for the design of DC-based clinical 
      trials.
FAU - Schumacher, Lana
AU  - Schumacher L
AD  - Division of Surgical Oncology, UCLA Medical Center, University of California Los 
      Angeles, USA.
FAU - Ribas, Antoni
AU  - Ribas A
FAU - Dissette, Vivian B
AU  - Dissette VB
FAU - McBride, William H
AU  - McBride WH
FAU - Mukherji, Bijay
AU  - Mukherji B
FAU - Economou, James S
AU  - Economou JS
FAU - Butterfield, Lisa H
AU  - Butterfield LH
LA  - eng
GR  - CA 16042/CA/NCI NIH HHS/United States
GR  - K12 CA 79605/CA/NCI NIH HHS/United States
GR  - K23 CA93376/CA/NCI NIH HHS/United States
GR  - R01 CA 77623/CA/NCI NIH HHS/United States
GR  - R01 CA 79976/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 Immunother
JT  - Journal of immunotherapy (Hagerstown, Md. : 1997)
JID - 9706083
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Immunoglobulins)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Peptides)
RN  - 0 (Protein Subunits)
RN  - 130068-27-8 (Interleukin-10)
RN  - 147205-72-9 (CD40 Ligand)
RN  - 187348-17-0 (Interleukin-12)
SB  - IM
MH  - Adenoviridae/*genetics
MH  - Antigens, CD
MH  - Antigens, Neoplasm/chemistry
MH  - CD40 Ligand/chemistry
MH  - Clinical Trials as Topic
MH  - Dendritic Cells/*cytology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - *Gene Transfer Techniques
MH  - Humans
MH  - Immunoglobulins/chemistry
MH  - Interleukin-10/chemistry
MH  - Interleukin-12/chemistry
MH  - Membrane Glycoproteins/chemistry
MH  - Peptides/chemistry
MH  - Phenotype
MH  - Protein Subunits/chemistry
MH  - T-Lymphocytes/chemistry/*immunology
MH  - T-Lymphocytes, Cytotoxic/metabolism
MH  - Time Factors
MH  - Transfection
MH  - Up-Regulation
MH  - CD83 Antigen
EDAT- 2004/04/13 05:00
MHDA- 2004/12/22 09:00
CRDT- 2004/04/13 05:00
PHST- 2004/04/13 05:00 [pubmed]
PHST- 2004/12/22 09:00 [medline]
PHST- 2004/04/13 05:00 [entrez]
AID - 00002371-200405000-00003 [pii]
AID - 10.1097/00002371-200405000-00003 [doi]
PST - ppublish
SO  - J Immunother. 2004 May-Jun;27(3):191-200. doi: 10.1097/00002371-200405000-00003.