Document Detail


Transfection of human monocyte-derived dendritic cells with native tumor DNA induces antigen-specific T-cell responses in vitro.
MedLine Citation:
PMID:  17172816     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Nucleofection of genomic tumor (Tu) DNA into human monocyte-derived dendritic cells (hMoDC) was evaluated for use in producing anti-tumor vaccines able to induce effective T-cell specific immune responses. METHODS: Cultured hMoDC obtained from HLA-A2+ normal donors were nucleofected with genomic DNA extracted from an HLA-A2+gp100+ Mel 526 cell line and 3' end-labeled with biotinylated TdT nucleotides or from a genetically-modified Mel 526 expressing enhanced green fluorescent protein (EGFP). An Amaxa Nucleofector system was used for electroporation. Nucleofected hMoDC were matured in the presence of cytokines and examined in ELISPOT assays for the ability to present the gp100(209-217) epitope to epitope-specific T cells or to prime autologous naïve T cells in culture. RESULTS: The nucleofected hMoDC presented gp100 protein to HLA-A2+gp 100-specific T cells as observed in IFN-gamma ELISPOT assays. Spot formation was inhibited by anti-HLA class I and HLA-A2 but not anti-HLA class II antibodies (Abs). Tu DNA-nucleofected hMoDC also primed nasmall yi, Ukrainianve autologous peripheral blood T cells in culture to develop into Tu-reactive effector cells (CTL). These CTL recognized Tu cells which had donated genomic DNA, and these responses were MHC class I- and class II-restricted. The CTL recognized shared Tu antigens encoded in Tu-derived DNA. CONCLUSION: Nucleofection of hMoDC with genomic Tu-derived DNA is a useful strategy for Tu vaccine production: it is feasible, does not require Tu epitope isolation, can be used when few Tu cells are available, and avoids Tu-induced DC suppression.
Authors:
Elisa Artusio; Bridget Hathaway; Joanna Stanson; Theresa L Whiteside
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2006-12-05
Journal Detail:
Title:  Cancer biology & therapy     Volume:  5     ISSN:  1538-4047     ISO Abbreviation:  Cancer Biol. Ther.     Publication Date:  2006 Dec 
Date Detail:
Created Date:  2007-02-01     Completed Date:  2007-05-24     Revised Date:  2007-12-03    
Medline Journal Info:
Nlm Unique ID:  101137842     Medline TA:  Cancer Biol Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1624-31     Citation Subset:  IM    
Affiliation:
Department of Pathology, University of Pittsburgh School of Medicine and Cancer Institute, Pittsburgh, Pennsylvania 15213-1863, USA.
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MeSH Terms
Descriptor/Qualifier:
Carcinoma, Squamous Cell
Cell Line, Tumor
Cell Survival
DNA, Neoplasm / genetics*
Dendritic Cells / cytology,  drug effects,  immunology*
Flow Cytometry
Genes, Reporter
Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
Green Fluorescent Proteins / genetics
HLA-A2 Antigen / immunology
Head and Neck Neoplasms
Humans
Interleukins / pharmacology
Melanoma
Plasmids
T-Lymphocytes / cytology,  drug effects,  immunology*
Transfection
Tumor Necrosis Factor-alpha / pharmacology
Grant Support
ID/Acronym/Agency:
R0-1 DE13918/DE/NIDCR NIH HHS
Chemical
Reg. No./Substance:
0/DNA, Neoplasm; 0/HLA-A2 Antigen; 0/Interleukins; 0/Tumor Necrosis Factor-alpha; 147336-22-9/Green Fluorescent Proteins; 83869-56-1/Granulocyte-Macrophage Colony-Stimulating Factor

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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