Engineered lentivector targeting of dendritic cells for in vivo immunization |
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Authors: | Yang Lili Yang Haiguang Rideout Kendra Cho Taehoon Joo Kye Il Ziegler Leslie Elliot Abigail Walls Anthony Yu Dongzi Baltimore David Wang Pin |
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Institution: | Division of Biology, California Institute of Technology, 1200 E. California Blvd, Pasadena, California 91125, USA. |
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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. |
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