Recombinant adenovirus vector activates and protects human monocyte-derived dendritic cells from apoptosis.
The aim of this study was to examine the effect of two of the most commonly used viral vectors, that is, retrovirus and adenovirus, on the antigen presentation of dendritic cells (DCs). DCs were generated from CD34(+) hematopoietic precursors and CD14(+) monocytes of the same prostate cancer patients. Adenoviral transduction of monocyte-derived DCs (MO-DCs) resulted in upregulation of CD80, CD86, and CD83 expression. Adenovirus-transduced MO-DCs were also more potent stimulators of allogeneic lymphocytes, produced increased amounts of the cytokines tumor necrosis factor alpha and interleukin 12 p70, and exhibited increased expression of NF-kappaB and antiapoptotic molecules Bcl-X(L) and Bcl-2. Enhanced expression of the antiapoptotic molecules correlated with increased resistance of adenovirus-transduced MO-DCs to spontaneous as well as Fas-mediated cell death. In contrast to the adenoviral construct, no significant transduction of MO-DCs with the retrovirus could be obtained. Transduction of CD34(+) cell-derived DCs with the retrovirus or the adenovirus did not significantly alter expression of the costimulatory molecules or cytokines studied. At lower stimulation ratios, CD34(+) cell-derived DCs transduced with retrovirus were less potent in their ability to stimulate allogeneic lymphocytes in comparison with nontransduced DCs. Our results indicate that adenoviral vectors may be more suitable for gene delivery to DCs for immunotherapy.
Lundqvist
Andreas
A
Immune and Gene Therapy, Department of Oncology and Pathology, Cancer Center Karolinska, Karolinska Institute, S-171 76 Stockholm, Sweden.
Choudhury
Aniruddha
A
Nagata
Takako
T
Andersson
Tove
T
Quinn
Gary
G
Fong
Timothy
T
Maitland
Norman
N
Pettersson
Sven
S
Paulie
Staffan
S
Pisa
Pavel
P
D000256:Adenoviridae; D017951:Antigen Presentation / Q000276:immunology*; D017209:Apoptosis / Q000235:genetics*; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology* / Q000502:physiology*; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D016328:NF-kappa B / Q000096:biosynthesis; D012190:Retroviridae; D014161:Transduction, Genetic; D015854:Up-Regulation
D016328:NF-kappa B