A single-component CD40-targeted adenovirus vector displays highly efficient transduction and activation of dendritic cells in a human skin substrate system.
Dendritic cell (DC) based tumor vaccination usually involves the administration of ex vivo generated autologous DC. Transduction of DC by viral vectors in vivo has been proposed as a more standardized and easily clinically applicable approach. Previously, we have reported that an Ad5 vector targeted to CD40 via genetic capsid incorporation of CD40L achieves selective transduction of DC in vitro. In the present study, we evaluate the ability of this vector to deliver transgenes in a stringent human substrate system. We report the capacity of this CD40-targeted vector to infect, with high efficiency, cutaneous DC resident in human skin explants, while simultaneously inducing their activation and maturation. This latest generation of single-component, fully targeted vectors should make feasible the clinical testing of in vivo DC-targeted vaccines.
Korokhov
Nikolay
N
VectorLogics, Inc., 550 11th Street South, Birmingham, Alabama 35294, USA. nkorokhov@vectorlogics.com
Noureddini
Sam C
SC
Curiel
David T
DT
Santegoets
Saskia J A M
SJ
Scheper
Rik J
RJ
de Gruijl
Tanja D
TD
D000256:Adenoviridae / Q000235:genetics; D019013:CD40 Antigens / Q000235:genetics* / Q000378:metabolism; D023201:CD40 Ligand; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D018390:Gene Targeting; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000008:administration & dosage; D006801:Humans; D007668:Kidney / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014161:Transduction, Genetic; D019076:Transgenes / Q000502:physiology
D019013:CD40 Antigens; D023201:CD40 Ligand