PMID- 15146294
OWN - NLM
STAT- MEDLINE
DCOM- 20041124
LR  - 20240426
IS  - 0340-7004 (Print)
IS  - 1432-0851 (Electronic)
IS  - 0340-7004 (Linking)
VI  - 53
IP  - 11
DP  - 2004 Nov
TI  - Strategies for antigen choice and priming of dendritic cells influence the 
      polarization and efficacy of antitumor T-cell responses in dendritic cell-based 
      cancer vaccination.
PG  - 963-77
AB  - Dendritic cells (DCs) primed with tumor antigens (Ags) can stimulate tumor 
      rejection. This study was aimed at evaluating the polarization of T-cell 
      responses using various DC Ag-priming strategies for vaccination purposes. DCs 
      cocultured with irradiated "apoptotic" tumor cells, DC-tumor fusions, and DCs 
      pulsed with freeze-thaw tumor lysate Ags served as Ag-primed DCs, with EG7 tumor 
      cells (class II negative) expressing OVA as the model Ag. DCs loaded with class 
      I- and class II-restricted OVA synthetic peptides served as controls. Primed DCs 
      were assessed by the in vitro activation of B3Z OVA-specific CD8 T cells and the 
      proliferation of OVA-specific CD8 and CD4 T cells from OT-I and OT-II TCR 
      transgenic mice, respectively. In vivo responses were measured by tumor 
      regression following treatment with Ag-primed DCs and by CTL assays. 
      Quantification of IL-2, IL-4, IL-5, IFN-gamma, and TNF-alpha by cytometric bead 
      array (CBA) assay determined the polarization of TH1/TH2 responses, whereas H-2 
      Kb/SIINFEKL tetramers monitored the expansion of OVA-specific T cells. DC-EG7 
      hybrids stimulated both efficient class I and class II OVA responses, showing 
      that DC-tumor hybrids are also capable of class II cross-presentation. The 
      hybrids also induced the most potent CTLs, offered the highest protection against 
      established EG7 tumors and also induced the highest stimulation of IFN-gamma and 
      TNF-alpha production. DCs cocultured with irradiated EG7 were also effective at 
      inducing OVA-specific responses, however with slightly reduced potency to those 
      evoked by the hybrids. DCs loaded with lysates Ags were much less efficient at 
      stimulating any of the OVA-specific T-cell responses, showed very little 
      antitumor protection, and stimulated a weak TH1 response, overbalanced by an IL-5 
      TH2 response. The strategy of Ag-loading clearly influences the ability of DCs to 
      polarize T cells for a TH1/TH2 response and thus determines the outcome of the 
      elicited immune response, during various vaccination protocols.
FAU - Galea-Lauri, Joanna
AU  - Galea-Lauri J
AD  - Department of Molecular Medicine, GKT School of Medicine, King's College London, 
      The Rayne Institute, 123 Coldharbour Lane, SE5 9NU, London, UK. 
      joanna.galea-lauri@kcl.ac.uk
FAU - Wells, James W
AU  - Wells JW
FAU - Darling, David
AU  - Darling D
FAU - Harrison, Phillip
AU  - Harrison P
FAU - Farzaneh, Farzin
AU  - Farzaneh F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20040514
PL  - Germany
TA  - Cancer Immunol Immunother
JT  - Cancer immunology, immunotherapy : CII
JID - 8605732
RN  - 0 (Antigens)
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (CD8 Antigens)
RN  - 0 (Cancer Vaccines)
RN  - 0 (Cytokines)
RN  - 0 (Interleukin-2)
RN  - 0 (Interleukin-5)
RN  - 0 (Peptides)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 207137-56-2 (Interleukin-4)
RN  - 82115-62-6 (Interferon-gamma)
RN  - 9006-59-1 (Ovalbumin)
SB  - IM
MH  - Animals
MH  - Antigens/chemistry
MH  - Antigens, Neoplasm/*chemistry
MH  - Apoptosis
MH  - CD8 Antigens/biosynthesis
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - *Cancer Vaccines
MH  - Cell Division
MH  - Cell Line, Tumor
MH  - Cell Separation
MH  - Cytokines/biosynthesis
MH  - Dendritic Cells/*immunology/metabolism
MH  - Flow Cytometry
MH  - Interferon-gamma/metabolism
MH  - Interleukin-2/metabolism
MH  - Interleukin-4/metabolism
MH  - Interleukin-5/metabolism
MH  - Lymphocytes/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Ovalbumin/metabolism
MH  - Peptides/chemistry
MH  - Recombinant Fusion Proteins/chemistry
MH  - T-Lymphocytes/cytology/*immunology
MH  - Th1 Cells
MH  - Tumor Necrosis Factor-alpha/metabolism
PMC - PMC11033009
EDAT- 2004/05/18 05:00
MHDA- 2004/12/16 09:00
PMCR- 2004/05/14
CRDT- 2004/05/18 05:00
PHST- 2003/11/19 00:00 [received]
PHST- 2004/03/17 00:00 [accepted]
PHST- 2004/05/18 05:00 [pubmed]
PHST- 2004/12/16 09:00 [medline]
PHST- 2004/05/18 05:00 [entrez]
PHST- 2004/05/14 00:00 [pmc-release]
AID - 542 [pii]
AID - 10.1007/s00262-004-0542-8 [doi]
PST - ppublish
SO  - Cancer Immunol Immunother. 2004 Nov;53(11):963-77. doi: 
      10.1007/s00262-004-0542-8. Epub 2004 May 14.