Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2006-1-23
pubmed:abstractText
The design and successful clinical implementation of cancer vaccines targeting the induction of T-cell mediated immunity is a rapidly evolving field that is hampered by an empirical selection of antigen and adjuvant. In particular, vaccines using defined tumor-associated peptide epitopes elicit only a restricted T-cell repertoire in a minority of patients. In this regard, vaccines comprising the whole spectrum of antigens presented by individual autologous tumors would be advantageous. In an in vitro model, we evaluated the capacity of naturally processed Epstein-Barr virus-transformed B-lymphoblastoid-cell line (LCL)-derived peptides to activate virus-specific CD8+ T cells of seropositive healthy individuals. While bulk peptides obtained by mild acid elution from LCL contained multiple T-cell epitopes, this complex mixture of peptides was poorly immunogenic, even when presented by mature dendritic cells (DC). Pretreatment of DC with proteasome inhibitors strongly enhanced the immunogenicity of single viral synthetic as well as bulk LCL peptides. This was most likely achieved by facilitating the loading of exogenous epitopes onto DC-associated HLA-class I complexes in the face of significant inter-peptide competition for such loading. Our results suggest that proteasome inhibitors may be used to increase the antigenicity of mature DC pulsed with exogenous synthetic or naturally processed peptide epitopes in vaccination trials.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-1759
pubmed:author
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
308
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
77-89
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Proteasome-inhibited dendritic cells demonstrate improved presentation of exogenous synthetic and natural HLA-class I peptide epitopes.
pubmed:affiliation
Department of Medicine III, Hematology and Oncology, Johannes Gutenberg-University of Mainz, Langenbeckstrasse 1, D-55101 Mainz, Germany.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't