TY - JOUR
T1 - Prolonged maturation and enhanced transduction of dendritic cells migrated from human skin explants after in situ delivery of CD40-targeted adenoviral vectors
AU - De Gruijl, Tanja D.
AU - Luykx-de Bakker, Sylvia A.
AU - Tillman, Bryan W.
AU - Van den Eertwegh, Alfons J.M.
AU - Buter, Jan
AU - Lougheed, Sinéad M.
AU - Van der Bij, Gerben J.
AU - Safer, A. Mahmoud
AU - Haisma, Hidde J.
AU - Curiel, David T.
AU - Scheper, Rik J.
AU - Pinedo, Herbert M.
AU - Gerritsen, Winald R.
PY - 2002/11/1
Y1 - 2002/11/1
N2 - Therapeutic tumor vaccination with viral vectors or naked DNA, carrying the genetic code for tumor-associated Ags, critically depends on the in vivo transduction of dendritic cells (DC). Transfection of predominantly nonprofessional APC and only small numbers of DC may hamper proper T cell activation. Aim of this study was, therefore, the targeted, selective, and enhanced in situ transduction of DC. A human skin explant model was used to explore targeted transduction of cutaneous DC after intradermal injection of a bispecific Ab conjugate to link adenoviral (Ad) vectors directly to CD40 on the DC surface. A significantly enhanced transduction efficiency and selectivity, and an increased activation state of migrating DC were thus achieved. Moreover, DC transduced by CD40-targeted Ad maintained their Ag-specific CTL-stimulatory ability for up to 1 wk after the start of migration, in contrast to DC transduced by untargeted Ad, which had lost this capacity by that time. Because DC targeting in vivo might obviate the need for the in vitro culture of autologous DC for adoptive transfer, CD40-targeted Ad vectors constitute a promising new vaccine modality for tumor immunotherapy.
AB - Therapeutic tumor vaccination with viral vectors or naked DNA, carrying the genetic code for tumor-associated Ags, critically depends on the in vivo transduction of dendritic cells (DC). Transfection of predominantly nonprofessional APC and only small numbers of DC may hamper proper T cell activation. Aim of this study was, therefore, the targeted, selective, and enhanced in situ transduction of DC. A human skin explant model was used to explore targeted transduction of cutaneous DC after intradermal injection of a bispecific Ab conjugate to link adenoviral (Ad) vectors directly to CD40 on the DC surface. A significantly enhanced transduction efficiency and selectivity, and an increased activation state of migrating DC were thus achieved. Moreover, DC transduced by CD40-targeted Ad maintained their Ag-specific CTL-stimulatory ability for up to 1 wk after the start of migration, in contrast to DC transduced by untargeted Ad, which had lost this capacity by that time. Because DC targeting in vivo might obviate the need for the in vitro culture of autologous DC for adoptive transfer, CD40-targeted Ad vectors constitute a promising new vaccine modality for tumor immunotherapy.
UR - http://www.scopus.com/inward/record.url?scp=0036840296&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.169.9.5322
DO - 10.4049/jimmunol.169.9.5322
M3 - Article
C2 - 12391253
AN - SCOPUS:0036840296
SN - 0022-1767
VL - 169
SP - 5322
EP - 5331
JO - Journal of Immunology
JF - Journal of Immunology
IS - 9
ER -