title: High efficiency transduction of dendritic cells by adenoviral vectors targeted to DC-SIGN.
abstract: Dendritic cells (DCs) are a central element in the development of antigen-specific immune responses. The lack of a specific and efficient technique for the in vivo delivery of antigens to DCs remains a major obstacle limiting a vaccine's ability to induce an effective immune response. The efficacy of adenoviral (Ad) vectors in this regard can be enhanced through alterations in vector tropism such that DC-targeted transduction is achieved. Here, the efficiency of DC transduction by Ad vectors retargeted to DC-specific ICAM-3 grabbing nonintegrin (DC-SIGN) was studied and compared to that of Ad vectors retargeted through CD40. A comparable and significant enhancement of gene transfer to monocyte derived DCs (MDDCs) was accomplished by means of an Ad vector harboring the Fc-binding domain of Staphylococcus aureus protein A in combination with antibodies to DC-SIGN or to CD40 or with fused complexes of human Ig-Fc with their natural ligands, i.e., ICAM-3 or CD40L, respectively. Whereas CD40-targeted Ad transduction resulted in a more profound phenotypic DC maturation, DC-SIGN- and CD40-targeted Ad both induced similar levels of IL-12 secretion. These data demonstrate the usefulness of DC-SIGN as a DC-restricted targeting motif for Ad-mediated vaccination strategies.
authors.affiliation: Vector Logics, Inc., Birmingham, Alabama 35233, USA. nkorokhov@vectorlogics.com
authors.forename: Nikolay
authors.initials: N
authors.lastname: Korokhov
authors.forename: Tanja D
authors.initials: TD
authors.lastname: de Gruijl
authors.forename: Wayne A
authors.initials: WA
authors.lastname: Aldrich
authors.forename: Pierre L
authors.initials: PL
authors.lastname: Triozzi
authors.forename: Papia T
authors.initials: PT
authors.lastname: Banerjee
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Gillies
authors.forename: Tyler J
authors.initials: TJ
authors.lastname: Curiel
authors.forename: Joanne T
authors.initials: JT
authors.lastname: Douglas
authors.forename: Rik J
authors.initials: RJ
authors.lastname: Scheper
authors.forename: David T
authors.initials: DT
authors.lastname: Curiel
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D019013:CD40 Antigens / Q000235:genetics; D019496:Cancer Vaccines / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology*; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D016219:Immunotherapy, Adoptive; D037181:Lectins, C-Type / Q000378:metabolism*; D009000:Monocytes / Q000276:immunology; D011956:Receptors, Cell Surface / Q000378:metabolism*; D014161:Transduction, Genetic / Q000379:methods*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D019013:CD40 Antigens; D019496:Cancer Vaccines; D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin