Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1998-5-14
pubmed:abstractText
DNA-based immunization strategies designed to elicit cellular antitumor immunity offer an attractive alternative to protein- or peptide-based approaches. In the present study we have evaluated the feasibility of DNA vaccination for the induction of CTL reactivity to five different melanoma Ags in vitro. Cultured, monocyte-derived dendritic cells (DC) were transiently transfected with plasmid DNA encoding human MART-1/Melan-A, pMel-17/gp100, tyrosinase, MAGE-1, or MAGE-3 by particle bombardment and used to stimulate autologous PBMC responder T cells. CTL reactivity to these previously identified melanoma Ags was reproducibly generated after two or three stimulations with genetically modified DC. Co-ordinate transfection of two melanoma Ag cDNAs into DC promoted CTL responders capable of recognizing epitopes from both gene products. Coinsertion of genes encoding the Th1-biasing cytokines IL-12 or IFN-alpha consistently enhanced the magnitude of the resulting Ag-specific CTL reactivity. Importantly, DC transfected with a single melanoma Ag cDNA were capable of stimulating Ag-specific CTL reactivity restricted by multiple host MHC alleles, some of which had not been previously identified. These results support the inherent strengths of gene-based vaccine approaches that do not require prior knowledge of responder MHC haplotypes or of relevant MHC-restricted peptide epitopes. Given previous observations of in situ tumor HLA allele-loss variants, DC gene vaccine strategies may elicit a greater diversity of host therapeutic immunity, thereby enhancing the clinical utility and success of such approaches.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Neoplasm, http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary, http://linkedlifedata.com/resource/pubmed/chemical/Epitopes, T-Lymphocyte, http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma, http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-12, http://linkedlifedata.com/resource/pubmed/chemical/Luciferases, http://linkedlifedata.com/resource/pubmed/chemical/MAGEA3 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/MART-1 Antigen, http://linkedlifedata.com/resource/pubmed/chemical/MLANA protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins, http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Peptides, http://linkedlifedata.com/resource/pubmed/chemical/SILV protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Vaccines, DNA, http://linkedlifedata.com/resource/pubmed/chemical/gp100 Melanoma Antigen
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
160
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1139-47
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:9570527-Antigens, Neoplasm, pubmed-meshheading:9570527-Cell Line, pubmed-meshheading:9570527-Cytotoxicity, Immunologic, pubmed-meshheading:9570527-DNA, Complementary, pubmed-meshheading:9570527-Dendritic Cells, pubmed-meshheading:9570527-Epitopes, T-Lymphocyte, pubmed-meshheading:9570527-Humans, pubmed-meshheading:9570527-Immunophenotyping, pubmed-meshheading:9570527-Interferon-gamma, pubmed-meshheading:9570527-Interleukin-12, pubmed-meshheading:9570527-Luciferases, pubmed-meshheading:9570527-MART-1 Antigen, pubmed-meshheading:9570527-Melanoma, pubmed-meshheading:9570527-Membrane Glycoproteins, pubmed-meshheading:9570527-Monocytes, pubmed-meshheading:9570527-Mutagenesis, Insertional, pubmed-meshheading:9570527-Neoplasm Proteins, pubmed-meshheading:9570527-Peptides, pubmed-meshheading:9570527-T-Lymphocytes, Cytotoxic, pubmed-meshheading:9570527-Th1 Cells, pubmed-meshheading:9570527-Transfection, pubmed-meshheading:9570527-Tumor Cells, Cultured, pubmed-meshheading:9570527-Vaccines, DNA, pubmed-meshheading:9570527-gp100 Melanoma Antigen
pubmed:year
1998
pubmed:articleTitle
Autologous human monocyte-derived dendritic cells genetically modified to express melanoma antigens elicit primary cytotoxic T cell responses in vitro: enhancement by cotransfection of genes encoding the Th1-biasing cytokines IL-12 and IFN-alpha.
pubmed:affiliation
Department of Surgery, University of Pittsburgh School of Medicine, University of Pittsburgh Cancer Institute, PA 15261, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't