High efficiency transduction of dendritic cells by adenoviral vectors targeted to DC-SIGN.
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.
Korokhov
Nikolay
N
Vector Logics, Inc., Birmingham, Alabama 35233, USA. nkorokhov@vectorlogics.com
de Gruijl
Tanja D
TD
Aldrich
Wayne A
WA
Triozzi
Pierre L
PL
Banerjee
Papia T
PT
Gillies
Stephen D
SD
Curiel
Tyler J
TJ
Douglas
Joanne T
JT
Scheper
Rik J
RJ
Curiel
David T
DT
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
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