rdf:type |
|
lifeskim:mentions |
umls-concept:C0023745,
umls-concept:C0079429,
umls-concept:C0376613,
umls-concept:C0378516,
umls-concept:C0679058,
umls-concept:C1517050,
umls-concept:C1547699,
umls-concept:C1627358,
umls-concept:C1706821,
umls-concept:C2349090,
umls-concept:C2349975,
umls-concept:C2700640
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pubmed:issue |
3
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pubmed:dateCreated |
2001-2-26
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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.
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pubmed:grant |
|
pubmed:language |
eng
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pubmed:journal |
|
pubmed:citationSubset |
IM
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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...
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
|
pubmed:issn |
0008-5472
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pubmed:author |
|
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
61
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pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
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pubmed:pagination |
1080-8
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pubmed:dateRevised |
2011-9-30
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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
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pubmed:year |
2001
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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.
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pubmed:affiliation |
Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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