Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2006-1-6
pubmed:abstractText
Fusogenic membrane glycoproteins (FMG) are a family of viral genes that, when expressed in tumour cells, trigger extensive cell to cell fusion and subsequent cell death. Gene therapy approaches using FMG are also potentially immunogenic, since syncitia generated ex vivo can be therapeutic as antitumour vaccines in murine models. This study has addressed the mechanisms responsible for the immunogenicity of FMG-mediated cell death, and its applicability to human immune priming. We show that fusion of human Mel888 melanoma cells following transfection with FMG can reverse the suppressive effects of Mel888 on dendritic cells (DC) phenotype, and potentiate IL-12 production by DC on activation in a cell contact-dependent manner. DC loaded with fusing, but not intact, tumour cells primed a naive, tumour-specific cytotoxic T-cell response, which was MHC class I-restricted and associated with production of high levels of IFNgamma and, later, IL-5. Fusing cells were an effective source of antigen for DC cross-priming and presentation of the melanoma-specific antigen gp100 to a specific T-cell clone. These data show, in a human system, that FMG represent an immunogenic, as well as cytotoxic, gene therapy for cancer, reversing the inhibitory effects of tumour cells on DC to potentiate IL-12 production and naive T-cell priming.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0969-7128
pubmed:author
pubmed:issnType
Print
pubmed:volume
13
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
138-49
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Fusogenic membrane glycoprotein-mediated tumour cell fusion activates human dendritic cells for enhanced IL-12 production and T-cell priming.
pubmed:affiliation
Cancer Research UK Clinical Center, St James's University Hospital, Leeds.
pubmed:publicationType
Journal Article