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Nat Biotechnol ; 26(3): 326-34, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18297056

ABSTRACT

We report a method of inducing antigen production in dendritic cells by in vivo targeting with lentiviral vectors that specifically bind to the dendritic cell-surface protein DC-SIGN. To target dendritic cells, we enveloped the lentivector with a viral glycoprotein from Sindbis virus engineered to be DC-SIGN-specific. In vitro, this lentivector specifically transduced dendritic cells and induced dendritic cell maturation. A high frequency (up to 12%) of ovalbumin (OVA)-specific CD8(+) T cells and a significant antibody response were observed 2 weeks after injection of a targeted lentiviral vector encoding an OVA transgene into naive mice. This approach also protected against the growth of OVA-expressing E.G7 tumors and induced regression of established tumors. Thus, lentiviral vectors targeting dendritic cells provide a simple method of producing effective immunity and may provide an alternative route for immunization with protein antigens.


Subject(s)
Cancer Vaccines/immunology , Dendritic Cells/immunology , Dendritic Cells/metabolism , Genetic Vectors/genetics , Lentivirus/genetics , Animals , B-Lymphocytes/cytology , B-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/cytology , CD8-Positive T-Lymphocytes/immunology , Cell Adhesion Molecules/metabolism , Cell Line , Dendritic Cells/cytology , Female , Gene Expression , Humans , Lectins, C-Type/metabolism , Mice , Mice, Inbred C57BL , Mice, Transgenic , Neoplasms, Experimental/immunology , Neoplasms, Experimental/therapy , Ovalbumin/genetics , Ovalbumin/immunology , Receptors, Cell Surface/metabolism , Sensitivity and Specificity , Sindbis Virus/genetics , Sindbis Virus/metabolism , Transduction, Genetic
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