High efficiency transduction of dendritic cells by adenoviral vectors targeted to DC-SIGN

Nikolay Korokhov, Tanja D. De Gruijl, Wayne A. Aldrich, Pierre L. Triozzi, Papia T. Banerjee, Stephen D. Gillies, Tyler J. Curiel, Joanne T. Douglas, Rik J. Scheper, David T. Curiel

Research output: Contribution to journalArticle

31 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)289-294
Number of pages6
JournalCancer Biology and Therapy
Volume4
Issue number3
DOIs
StatePublished - Mar 2005
Externally publishedYes

Keywords

  • Antigen presentation/processing
  • Cell activation
  • Cell surface molecules
  • Dendritic cells
  • Gene therapy

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

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