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MRNA-transfected Dendritic Cells Expressing Polypeptides That Link MHC-I Presentation to Constitutive TLR4 Activation Confer Tumor Immunity.


ABSTRACT: Recently, we have developed a novel genetic platform for improving dendritic cell (DC) induction of peptide-specific CD8 T cells, based on membrane-anchored β2-microglobulin (β2m) linked to a selected antigenic peptide at its N-terminus and to the cytosolic domain of toll-like receptor (TLR)4 C-terminally. In vitro transcribed mRNA transfection of antigen presenting cells resulted in polypeptides that efficiently coupled peptide presentation to cellular activation. In the present study, we evaluated the immunogenicity of such constructs in mRNA-transfected immature murine bone marrow-derived DCs. We show that the encoded peptide β2m-TLR4 products were expressed at the cell surface up to 72 hours and stimulated the maturation of DCs. In vivo, these DCs prompted efficient peptide-specific T-

SUBMITTER: Cafri G 

PROVIDER: S-EPMC4817861 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature