Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2001-2-26
pubmed:abstractText
Recently, Flt3 (Fms-like tyrosine kinase 3)-ligand has been identified as an important cytokine for the generation of professional antigen-presenting cells (APCs), particularly dendritic cells (DCs). A recombinant chimera of the extracellular domain of Flt3-ligand (FL) linked to a model antigen may potentially target the antigen to DCs and their precursor cells. Using human papillomavirus-16 E7 as a model antigen, we evaluated the effect of linkage to FL on the potency of antigen-specific immunity generated by naked DNA vaccines administered intradermally via gene gun. We found that vaccines containing chimeric FL-E7 fusion genes significantly increased the frequency of E7-specific CD8+ T cells relative to vaccines containing the wild-type E7 gene. In vitro studies indicated that cells transfected with FL-E7 DNA presented E7 antigen through the MHC class I pathway more efficiently than wild-type E7 DNA. Furthermore, bone marrow-derived DCs pulsed with cell lysates containing FL-E7 fusion protein presented E7 antigen through the MHC class I pathway more efficiently than DCs pulsed with cell lysates containing wild-type E7 protein. More importantly, this fusion converted a less effective vaccine into one with significant potency against established E7-expressing metastatic tumors. The FL-E7 fusion vaccine mainly targeted CD8+ T cells, and antitumor effects were completely CD4 independent. These results indicate that fusion of a gene encoding the extracellular domain of FL to an antigen gene may greatly enhance the potency of DNA vaccines via CD8-dependent pathways.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Viral, http://linkedlifedata.com/resource/pubmed/chemical/Cancer Vaccines, http://linkedlifedata.com/resource/pubmed/chemical/Epitopes, T-Lymphocyte, http://linkedlifedata.com/resource/pubmed/chemical/Histocompatibility Antigens Class I, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Oncogene Proteins, Viral, http://linkedlifedata.com/resource/pubmed/chemical/Papillomavirus E7 Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Vaccines, DNA, http://linkedlifedata.com/resource/pubmed/chemical/flt3 ligand protein, http://linkedlifedata.com/resource/pubmed/chemical/oncogene protein E7, Human...
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
61
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1080-8
pubmed:dateRevised
2011-9-30
pubmed:meshHeading
pubmed-meshheading:11221836-Animals, pubmed-meshheading:11221836-Antigen Presentation, pubmed-meshheading:11221836-Antigens, Viral, pubmed-meshheading:11221836-CD4-Positive T-Lymphocytes, pubmed-meshheading:11221836-CD8-Positive T-Lymphocytes, pubmed-meshheading:11221836-Cancer Vaccines, pubmed-meshheading:11221836-Dendritic Cells, pubmed-meshheading:11221836-Endoplasmic Reticulum, pubmed-meshheading:11221836-Epitopes, T-Lymphocyte, pubmed-meshheading:11221836-Female, pubmed-meshheading:11221836-Genetic Linkage, pubmed-meshheading:11221836-Histocompatibility Antigens Class I, pubmed-meshheading:11221836-Humans, pubmed-meshheading:11221836-Immunotherapy, Active, pubmed-meshheading:11221836-Lung Neoplasms, pubmed-meshheading:11221836-Major Histocompatibility Complex, pubmed-meshheading:11221836-Membrane Proteins, pubmed-meshheading:11221836-Mice, pubmed-meshheading:11221836-Mice, Inbred C57BL, pubmed-meshheading:11221836-Oncogene Proteins, Viral, pubmed-meshheading:11221836-Papillomavirus E7 Proteins, pubmed-meshheading:11221836-Protein Structure, Tertiary, pubmed-meshheading:11221836-Recombinant Fusion Proteins, pubmed-meshheading:11221836-Vaccines, DNA
pubmed:year
2001
pubmed:articleTitle
Enhancement of DNA vaccine potency by linkage of antigen gene to a gene encoding the extracellular domain of Fms-like tyrosine kinase 3-ligand.
pubmed:affiliation
Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't