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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2001-2-22
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pubmed:abstractText |
Self-replicating RNA vaccines (RNA replicons) have emerged as an attractive approach for tumor immunotherapy. RNA replicons do not integrate into host chromosomes, eliminating the concern for oncogenicity associated with a DNA vaccine. In this study, we used human papillomavirus type 16 (HPV-16) E7 as a model antigen and evaluated E7-specific immunity generated by a Sindbis virus self-replicating RNA vector, SIN-rep5. Three different constructs were created to target E7 antigen to different cellular localizations: (1) E7, a cytosolic/nuclear protein; (2) Sig/E7, a secretory protein; (3) Sig/E7/LAMP-1, in which we linked the transmembrane and cytoplasmic regions of the lysosome-associated membrane protein 1 (LAMP-1) to E7 protein to target E7 to the endosomal/lysosomal compartment. We found that the RNA replicon vaccine containing the Sig/E7/LAMP-1 fusion gene generated the highest E7-specific T cell-mediated immune responses and antitumor effects relative to RNA vaccines containing either wild-type E7 or Sig/E7. Our in vitro studies demonstrated that E7 antigen from Sig/E7/LAMP-1 RNA replicon-transfected apoptotic cells can be taken up by bone marrow-derived dendritic cells (DCs) and presented more efficiently through the MHC class I pathway than wild-type E7 RNA replicon-transfected apoptotic cells. Furthermore, our data revealed that CD8(+) T cells, CD4(+) T cells, and NK cells were important for the antitumor effects generated by Sig/E7/LAMP-1 RNA vaccination. These results indicate that targeting antigen to the endosomal/lysosomal compartment via fusion to LAMP-1 may greatly enhance the potency of self-replicating RNA vaccines.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Cancer Vaccines,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/Lysosome-Associated Membrane...,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Oncogene Proteins, Viral,
http://linkedlifedata.com/resource/pubmed/chemical/Papillomavirus E7 Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Vaccines, DNA,
http://linkedlifedata.com/resource/pubmed/chemical/oncogene protein E7, Human...
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1043-0342
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
10
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pubmed:volume |
12
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
235-52
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:11177561-Animals,
pubmed-meshheading:11177561-Antigens, CD,
pubmed-meshheading:11177561-Apoptosis,
pubmed-meshheading:11177561-Bone Marrow Cells,
pubmed-meshheading:11177561-CD4-Positive T-Lymphocytes,
pubmed-meshheading:11177561-CD8-Positive T-Lymphocytes,
pubmed-meshheading:11177561-Cancer Vaccines,
pubmed-meshheading:11177561-Cell Line,
pubmed-meshheading:11177561-Cell Membrane,
pubmed-meshheading:11177561-Cricetinae,
pubmed-meshheading:11177561-DNA,
pubmed-meshheading:11177561-Dendritic Cells,
pubmed-meshheading:11177561-Endosomes,
pubmed-meshheading:11177561-Enzyme-Linked Immunosorbent Assay,
pubmed-meshheading:11177561-Female,
pubmed-meshheading:11177561-Flow Cytometry,
pubmed-meshheading:11177561-Genes, MHC Class I,
pubmed-meshheading:11177561-Humans,
pubmed-meshheading:11177561-In Situ Nick-End Labeling,
pubmed-meshheading:11177561-Killer Cells, Natural,
pubmed-meshheading:11177561-Lysosome-Associated Membrane Glycoproteins,
pubmed-meshheading:11177561-Lysosomes,
pubmed-meshheading:11177561-Membrane Glycoproteins,
pubmed-meshheading:11177561-Mice,
pubmed-meshheading:11177561-Mice, Inbred C57BL,
pubmed-meshheading:11177561-Neoplasms,
pubmed-meshheading:11177561-Oncogene Proteins, Viral,
pubmed-meshheading:11177561-Papillomavirus E7 Proteins,
pubmed-meshheading:11177561-Phagocytosis,
pubmed-meshheading:11177561-Plasmids,
pubmed-meshheading:11177561-Sindbis Virus,
pubmed-meshheading:11177561-Spleen,
pubmed-meshheading:11177561-T-Lymphocytes, Cytotoxic,
pubmed-meshheading:11177561-Time Factors,
pubmed-meshheading:11177561-Transfection,
pubmed-meshheading:11177561-Vaccines, DNA
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pubmed:year |
2001
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pubmed:articleTitle |
Enhancement of sindbis virus self-replicating RNA vaccine potency by targeting antigen to endosomal/lysosomal compartments.
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pubmed:affiliation |
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD 21205, 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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