PMID- 15753654 OWN - NLM STAT- MEDLINE DCOM- 20060321 LR - 20210102 IS - 1538-4047 (Print) IS - 1538-4047 (Linking) VI - 4 IP - 3 DP - 2005 Mar TI - High efficiency transduction of dendritic cells by adenoviral vectors targeted to DC-SIGN. PG - 289-94 AB - 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. FAU - Korokhov, Nikolay AU - Korokhov N AD - Vector Logics, Inc., Birmingham, Alabama 35233, USA. nkorokhov@vectorlogics.com FAU - de Gruijl, Tanja D AU - de Gruijl TD FAU - Aldrich, Wayne A AU - Aldrich WA FAU - Triozzi, Pierre L AU - Triozzi PL FAU - Banerjee, Papia T AU - Banerjee PT FAU - Gillies, Stephen D AU - Gillies SD FAU - Curiel, Tyler J AU - Curiel TJ FAU - Douglas, Joanne T AU - Douglas JT FAU - Scheper, Rik J AU - Scheper RJ FAU - Curiel, David T AU - Curiel DT LA - eng GR - R01 CA 86811/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20050320 PL - United States TA - Cancer Biol Ther JT - Cancer biology & therapy JID - 101137842 RN - 0 (CD40 Antigens) RN - 0 (Cancer Vaccines) RN - 0 (Cell Adhesion Molecules) RN - 0 (DC-specific ICAM-3 grabbing nonintegrin) RN - 0 (Lectins, C-Type) RN - 0 (Receptors, Cell Surface) SB - IM MH - Adenoviridae/*genetics MH - CD40 Antigens/genetics MH - Cancer Vaccines/genetics MH - Cell Adhesion Molecules/*metabolism MH - Cell Line MH - Dendritic Cells/*immunology MH - Genetic Vectors/*genetics MH - Humans MH - Immunotherapy, Adoptive MH - Lectins, C-Type/*metabolism MH - Monocytes/immunology MH - Receptors, Cell Surface/*metabolism MH - Transduction, Genetic/*methods EDAT- 2005/03/09 09:00 MHDA- 2006/03/22 09:00 CRDT- 2005/03/09 09:00 PHST- 2005/03/09 09:00 [pubmed] PHST- 2006/03/22 09:00 [medline] PHST- 2005/03/09 09:00 [entrez] AID - 1499 [pii] AID - 10.4161/cbt.4.3.1499 [doi] PST - ppublish SO - Cancer Biol Ther. 2005 Mar;4(3):289-94. doi: 10.4161/cbt.4.3.1499. Epub 2005 Mar 20.