https://scholars.lib.ntu.edu.tw/handle/123456789/458694
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.author | WEN-FANG CHENG | en_US |
dc.contributor.author | Hung C.-F. | en_US |
dc.contributor.author | Hsu K.-F. | en_US |
dc.contributor.author | Chai C.-Y. | en_US |
dc.contributor.author | He L. | en_US |
dc.contributor.author | Ling M. | en_US |
dc.contributor.author | Slater L.A. | en_US |
dc.contributor.author | Roden R.B.S. | en_US |
dc.contributor.author | Wu T.-C. | en_US |
dc.creator | Wen-Fang Cheng;Hung C.-F.;Hsu K.-F.;Chai C.-Y.;He L.;Ling M.;Slater L.A.;Roden R.B.S.;Wu T.-C. | - |
dc.date.accessioned | 2020-02-14T02:50:26Z | - |
dc.date.available | 2020-02-14T02:50:26Z | - |
dc.date.issued | 2001 | - |
dc.identifier.issn | 1043-0342 | - |
dc.identifier.uri | 2-s2.0-0035835376 | - |
dc.identifier.uri | https://scholars.lib.ntu.edu.tw/handle/123456789/458694 | - |
dc.description.abstract | 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. | - |
dc.relation.ispartof | Human Gene Therapy | - |
dc.subject.classification | [SDGs]SDG3 | - |
dc.subject.other | DNA vaccine; major histocompatibility antigen class 1; membrane protein; virus antigen; virus vaccine; animal cell; animal experiment; antineoplastic activity; article; cancer immunotherapy; controlled study; dendritic cell; drug potency; endosome; female; fusion gene; gene targeting; immune response; lysosome; mouse; natural killer cell; nonhuman; replicon; Sindbis virus; T lymphocyte; virus replication; Wart virus; Animals; Antigens, CD; Apoptosis; Bone Marrow Cells; Cancer Vaccines; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cell Line; Cell Membrane; Cricetinae; Dendritic Cells; DNA; Endosomes; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; Genes, MHC Class I; Humans; In Situ Nick-End Labeling; Killer Cells, Natural; Lysosome-Associated Membrane Glycoproteins; Lysosomes; Membrane Glycoproteins; Mice; Mice, Inbred C57BL; Neoplasms; Oncogene Proteins, Viral; Phagocytosis; Plasmids; Sindbis Virus; Spleen; T-Lymphocytes, Cytotoxic; Time Factors; Transfection; Vaccines, DNA; Animalia; Human papillomavirus; Human papillomavirus type 16; Human papillomavirus types; Sindbis virus | - |
dc.title | Enhancement of sindbis virus self-replicating RNA vaccine potency by targeting antigen to endosomal/lysosomal compartments | en_US |
dc.type | journal article | en |
dc.identifier.doi | 10.1089/10430340150218387 | - |
dc.identifier.scopus | 56601533000 | - |
dc.relation.pages | 235-252 | - |
dc.relation.journalvolume | 12 | - |
dc.relation.journalissue | 3 | - |
item.openairetype | journal article | - |
item.fulltext | no fulltext | - |
item.openairecristype | http://purl.org/coar/resource_type/c_6501 | - |
item.grantfulltext | none | - |
item.cerifentitytype | Publications | - |
crisitem.author.dept | Obstetrics & Gynecology | - |
crisitem.author.dept | Obstetrics & Gynecology-NTUH | - |
crisitem.author.dept | Clinical Medicine | - |
crisitem.author.dept | Oncology | - |
crisitem.author.dept | Surgery-NTUCC | - |
crisitem.author.orcid | 0000-0002-3282-6304 | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | National Taiwan University Hospital | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | College of Medicine | - |
crisitem.author.parentorg | National Taiwan University Cancer Center (NTUCC) | - |
顯示於: | 醫學系 |
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