Viral vectors for dendritic cell-based immunotherapy

Jenne, Lars; Schuler, Gerold; Steinkasserer, Alexander

doi:10.1016/s1471-4906(00)01813-5

Cited by 157 publications

(94 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In general, DCs generated from adherent celldepleted PB monocytes are used for the development of gene-modified DC vaccines that express known tumor antigens, using either non-viral or viral vectors. 7,9,10,[31][32][33] We, and others, have shown the potential of HIV-1-based lentiviral vectors in delivering transgene to human monocyte-derived DCs and the induction of T-cell responses. 25,[34][35][36] The initial aim of the current study was to develop and optimize a clinically feasible method to generate gene-modified DC vaccines using an SIN lentiviral vector for cancer immunotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…6 Recently, therapeutic vaccination with genetically modified DCs expressing TAA or viral antigens has been shown to be an efficient strategy to induce immunity against malignancy and infectious diseases. [7][8][9][10][11] Genetic modification of DC with TAA genes could allow stable antigen expression as well as presentation of multiple and cryptic epitopes by both major histocompatability complex (MHC) class I and class II molecules. 11,12 In general, DCs are generated ex vivo either from CD34 + progenitor cells or peripheral blood (PB) monocytes by culturing them in culture medium containing a defined cytokine cocktail.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Ex vivo generation of genetically modified dendritic cells for immunotherapy: implications of lymphocyte contamination

et al. 2005

View full text Add to dashboard Cite

Genetically modified dendritic cell (DC) vaccines expressing tumor-associated antigens are currently used for cancer immunotherapy. Peripheral blood (PB) monocyte precursors are a relatively convenient source of DCs for use in clinical studies, but are often contaminated by lymphocytes. The current study was conducted to examine the impact of Tlymphocyte contamination on genetically modified DC product. PB monocyte-derived DCs were efficiently transduced (75-95%) with an HIV-1-based self-inactivating lentiviral vector encoding a model antigen, the enhanced green fluorescent protein (eGFP). The lymphocyte-free DC culture transduced with Lenti-eGFP showed stable expression of eGFP without measurable decline in viability. In contrast, the eGFP-positive DCs disappeared rapidly in transduced DC cultures containing lymphocyte contaminants, concurrent with detectable activation and expansion of T-lymphocytes. Upon antigen recall, these T cells elicited major histocompatability complex-restricted antigen-specific cytotoxicity against eGFP-positive autologous DCs and mitogen-stimulated T lymphoblasts, mainly through the perforin-mediated pathway. In summary, this study demonstrate that the relative purity of DC cultures could determine the persistence of gene-modified DC, which may affect the induction of effective immune responses by DC vaccination strategies. Gene Therapy (2005) 12, 259-271.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Ex vivo generation of genetically modified dendritic cells for immunotherapy: implications of lymphocyte contamination

et al. 2005

View full text Add to dashboard Cite

show abstract

“…These differences have been related to the state of maturation, preparations of DC from different anatomical compartments, and generation of DCs using different species. Because viral gene transfer strategies are required to achieve high transduction rates in human but not murine DC (24), it is particularly important that the differences between murine and human DC populations are also reflected in the capacity to express transduced genes (40,41).…”

Section: Discussionmentioning

confidence: 99%

“…However, it has not been determined whether human DC can be efficiently transduced by FasL and whether these cells are capable to eliminate Fas ϩ target cells. In contrast to murine cells or cell lines, transduction of human monocyte-derived macrophages and DC is difficult, and high transduction rates could be achieved only with viral gene transfer strategies (24). In addition, in previous studies, FasL-expressing APC were generated from mice deficient in Fas-mediated apoptosis to prevent self-destruction of transduced FasL-expressing APC.…”

Section: Endritic Cells (Dc)mentioning

confidence: 99%

Mature But Not Immature Fas Ligand (CD95L)-Transduced Human Monocyte-Derived Dendritic Cells Are Protected from Fas-Mediated Apoptosis and Can Be Used as Killer APC

Hoves

Krause²,

Halbritter³

et al. 2003

The Journal of Immunology

View full text Add to dashboard Cite

Several in vitro and animal studies have been performed to modulate the interaction of APCs and T cells by Fas (CD95/Apo-1) signaling to delete activated T cells in an Ag-specific manner. However, due to the difficulties in vector generation and low transduction frequencies, similar studies with primary human APC are still lacking. To evaluate whether Fas ligand (FasL/CD95L) expressing killer APC could be generated from primary human APC, monocyte-derived dendritic cells (DC) were transduced using the inducible Cre/Loxp adenovirus vector system. Combined transduction of DC by AdLoxpFasL and AxCANCre, but not single transduction with these vectors, resulted in dose- and time-dependent expression of FasL in >70% of mature DC (mDC), whereas <20% of immature DC (iDC) expressed FasL. In addition, transduction by AdLoxpFasL and AxCANCre induced apoptosis in >80% of iDC, whereas FasL-expressing mDC were protected from FasL/Fas (CD95/Apo-1)-mediated apoptosis despite coexpression of Fas. FasL-expressing mDC eliminated Fas+ Jurkat T cells as well as activated primary T cells by apoptosis, whereas nonactivated primary T cells were not deleted. Induction of apoptosis in Fas+ target cells required expression of FasL in DC and cell-to-cell contact between effector and target cell, and was not dependent on soluble FasL. Induction of apoptosis in Fas+ target cells required expression of FasL in DC, cell-to-cell contact between effector and target cell, and was not dependent on soluble FasL. The present results demonstrate that FasL-expressing killer APC can be generated from human monocyte-derived mDC using adenoviral gene transfer. Our results support the strategy to use killer APCs as immunomodulatory cells for the treatment of autoimmune disease and allograft rejection.

show abstract

“…At a cellular level in particular, DC, the sentinels of the immune system, are targeted by numerous viral strategies aiming to inhibit an anti-viral immune response [28]. Recent analysis of VV-infected DC have revealed several new viral mechanisms that perturb important functions of DC [29]. Accordingly, it was shown that even though VV effectively infects DC, only viral genes regulated by early and (though to a far lesser degree) early intermediate genes were expressed in monocyte-derived DC, and thus no viral replication occurs in human DC [30].…”

Section: Introductionmentioning

confidence: 99%

Vaccinia virus impairs directional migration and chemokine receptor switch of human dendritic cells

Humrich¹,

Thumann²,

Greiner³

et al. 2007

Eur J Immunol

Self Cite

View full text Add to dashboard Cite

A crucial event for the induction of an anti-viral immune response is the coordinated, phenotype-dependent migration of dendritic cells (DC) to sites of infection and secondary lymphoid organs. Here we show that the vaccinia virus (VV) strains Western Reserve (WR) and modified virus Ankara (MVA) inhibit directional migration of mature DC toward the lymphoid chemokines CCL19 and CXCL12 without affecting surface expression of the respective chemokine receptors or impairing undirected cellular locomotion. Instead, infection with VV results in a deficiency of extracellular signalregulated kinase-1 and a disturbance of intracellular calcium mobilization, indicating a viral interference with signaling events downstream of the surface chemokine receptors. In immature DC, apart from inhibiting chemokine-induced migration of infected DC, infection with both VV strains increases expression of the inflammatory chemokine receptors CCR1 and CXCR1 on non-infected bystander DC, which depends on the activity of IFN-a. Although functional, these chemokine receptors are resistant to lipopolysaccharide-induced down-regulation. In addition, VV-infected and noninfected bystander DC fail to up-regulate the lymphoid chemokine receptor CCR7 upon activation, together pointing to a disability to undergo the chemokine receptor switch. This study shows that VV targets directional migration of professional antigenpresenting cells at multiple functional levels, revealing a potent viral strategy of immune escape.See accompanying commentary: http://dx

show abstract

Viral vectors for dendritic cell-based immunotherapy

Cited by 157 publications

References 44 publications

Ex vivo generation of genetically modified dendritic cells for immunotherapy: implications of lymphocyte contamination

Ex vivo generation of genetically modified dendritic cells for immunotherapy: implications of lymphocyte contamination

Mature But Not Immature Fas Ligand (CD95L)-Transduced Human Monocyte-Derived Dendritic Cells Are Protected from Fas-Mediated Apoptosis and Can Be Used as Killer APC

Vaccinia virus impairs directional migration and chemokine receptor switch of human dendritic cells

Contact Info

Product

Resources

About