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• W1988136894 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." @default.
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• W1988136894 date "2001-02-10" @default.
• W1988136894 modified "2023-10-16" @default.
• W1988136894 title "Enhancement of Sindbis Virus Self-Replicating RNA Vaccine Potency by Targeting Antigen to Endosomal/Lysosomal Compartments" @default.
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• W1988136894 doi "https://doi.org/10.1089/10430340150218387" @default.
• W1988136894 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/11177561" @default.
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