Linked Life Data

15034075

Source:http://linkedlifedata.com/resource/pubmed/id/15034075

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2004-3-22
pubmed:abstractText
We describe in this study a strategy to produce synthetic vaccines based on a single polypeptide capable of eliciting strong immune responses to a combination CTL and Th epitopes with the purpose of treating malignancies or preventing infectious diseases. This strategy is based on the capacity of Trojan Ags to deliver exogenous Ags into the intracellular compartments, where processing into MHC-binding peptides takes place. Our previous work demonstrated that Trojan Ags containing a CTL epitope localized to intracellular compartments, where MHC class I-binding peptides were generated in a TAP-independent fashion by the action of various exopeptidases and the endopeptidase furin. In this study, we report that Trojan Ags containing several CTL epitopes joined via furin-sensitive linkers generated all of the corresponding MHC class I-binding peptides, which were recognized by CTL. However, Trojan Ags prepared with furin-resistant linkers failed to produce the MHC class I-binding peptides. We also present data indicating that Trojan Ags bearing both CTL and Th epitopes can generate the corresponding MHC class I- and II-binding peptides, which are capable of stimulating T cell responses. Most significantly, in vivo vaccination of mice with a single injection of multiepitope Trojan Ags resulted in strong CTL and Th responses that translated into significant antitumor responses in a model of malignant melanoma. The overall results indicate that Trojan Ags prepared with furin-sensitive linkers are ideal candidates for producing synthetic multiepitope vaccines for the induction of CTL and Th responses that could be used against a variety of diseases, including cancer.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
172
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4575-82
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:15034075-Animals, pubmed-meshheading:15034075-Antigen Presentation, pubmed-meshheading:15034075-Antigen-Presenting Cells, pubmed-meshheading:15034075-Cancer Vaccines, pubmed-meshheading:15034075-Cell Line, Tumor, pubmed-meshheading:15034075-Cytotoxicity, Immunologic, pubmed-meshheading:15034075-Egg Proteins, pubmed-meshheading:15034075-Epitopes, T-Lymphocyte, pubmed-meshheading:15034075-Female, pubmed-meshheading:15034075-Furin, pubmed-meshheading:15034075-Injections, Subcutaneous, pubmed-meshheading:15034075-Mastocytoma, pubmed-meshheading:15034075-Melanoma, Experimental, pubmed-meshheading:15034075-Mice, pubmed-meshheading:15034075-Mice, Inbred C57BL, pubmed-meshheading:15034075-Mice, Transgenic, pubmed-meshheading:15034075-Neoplasm Transplantation, pubmed-meshheading:15034075-Ovalbumin, pubmed-meshheading:15034075-Peptide Fragments, pubmed-meshheading:15034075-T-Lymphocytes, Cytotoxic, pubmed-meshheading:15034075-T-Lymphocytes, Helper-Inducer, pubmed-meshheading:15034075-Transfection, pubmed-meshheading:15034075-Vaccines, Subunit
pubmed:year
2004
pubmed:articleTitle
Multiepitope Trojan antigen peptide vaccines for the induction of antitumor CTL and Th immune responses.
pubmed:affiliation
Department of Immunology and Cancer Center, Mayo College of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't