Contrasting Effects of Human, Canine, and Hybrid Adenovirus Vectors on the Phenotypical and Functional Maturation of Human Dendritic Cells: Implications for Clinical Efficacy

Perreau, Matthieu; Mennechet, Franck J. D.; Serratrice, Nicolas; Glasgow, Joel N.; Curiel, David T.; Wodrich, Harald; Kremer, Eric J.

doi:10.1128/jvi.01530-06

Cited by 52 publications

(60 citation statements)

References 90 publications

(114 reference statements)

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“…38 Previous studies revealed divergent data on DC maturation by replication-deficient adenovirus vectors, dependent on the DC preparation, species from which the DCs originated and experimental setting. 37 How oncolytic adenoviruses affect human DC maturation, however, has not been reported. We hypothesized that the induction of potent DC maturation by oncolytic adenoviruses is advantageous for the induction of anti-cancer immunity during adenoviral oncolysis.…”

Section: Expression Of Mhc Molecules Costimulatory Molecules and Secmentioning

confidence: 99%

“…Poor internalization, endosomal escape, intracellular trafficking, or nuclear transfer of the virus genome might be responsible for incomplete transduction after virus binding/uptake into 100% of the cells. 37 To determine viral cytotoxicity, we infected cells with serial 10-fold dilutions of oncolytic adenoviruses (Ad5.2xTyr or Ad5/3.2xTyr) or control adenoviruses (Ad5wt, Ad5/3, or AdTL) followed by crystal violet staining of surviving cells (Fig. 3b) or by MTS assay (Fig.…”

Section: Adenoviral Transduction Of Immature and Mature Dcsmentioning

confidence: 99%

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Modulation of viability and maturation of human monocyte‐derived dendritic cells by oncolytic adenoviruses

Schierer

Hesse

Müller

et al. 2007

Intl Journal of Cancer

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Adenoviral oncolysis is a promising new modality for treatment of cancer based on selective viral replication in tumor cells. However, tumor cell killing by adenoviral oncolysis needs to be improved to achieve therapeutic benefit in the clinic. Towards this end, the activation of anti-tumor immunity by adenoviral oncolysis might constitute a potent mechanism for systemic killing of uninfected tumor cells, thereby effectively complementing direct tumor cell killing by the virus. Knowledge of anti-tumor immune induction by adenoviral oncolysis, however, is lacking mostly due to species-specificity of adenovirus replication, which has hampered studies of human oncolytic adenoviruses in animals. We suggest the analysis of interactions of oncolytic adenoviruses with human immune cells as rational basis for the implementation of adenoviral oncolysis-induced anti-tumor immune activation. The goal of our study was to investigate how oncolytic adenoviruses affect human dendritic cells (DCs), key regulators of innate and adoptive immunity that are widely investigated as tumor vaccines. We report that melanoma-directed oncolytic adenoviruses, like replication-deficient adenoviruses but unlike adenoviruses with unrestricted replication potential, are not toxic to monocytederived immature DCs and do not block DC maturation by external stimuli. Of note, this is in contrast to reports for other viruses/ viral vectors and represents a prerequisite for anti-tumor immune activation by adenoviral oncolysis. Furthermore, we show that these oncolytic adenoviruses alone do not or only partially induce DC maturation. Thus additional signals are required for optimal immune activation. These could be delivered, for example, by inserting immunoregulatory transgenes into the oncolytic adenovirus genome. ' 2007 Wiley-Liss, Inc.Key words: oncolytic adenovirus; dendritic cell; DC maturation; virotherapy; tumor vaccination Oncolytic adenoviruses are emerging agents for the treatment of cancer based on tumor cell killing by virus infection, replication, cell lysis and spread. 1,2 Tumor-selectivity of virus replication is pivotal for this therapeutic strategy and has been achieved for oncolytic adenoviruses by (i) the mutation of adenoviral genes that are required for viral replication in normal cells, but which are dispensable in tumor cells, and (ii) the expression of essential viral genes, mostly of E1A, from heterologous, tumor-selective promoters. 1 Importantly, the advanced knowledge of the adenovirus structure, genome and replication cycle facilitates molecular modifications to the virus that are required or beneficial for therapeutic applications: besides the introduction of tumor-selective replication and cell killing potential, these are the modification of the virus tropism, or the expression of therapeutic genes. 3,4 Oncolytic adenoviruses have shown promise in clinical trials, which demonstrated proof-of-concept for tumor-selective virus replication and a favorable safety profile. 5,6 However, therapeutic efficacy of the investigat...

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Section: Expression Of Mhc Molecules Costimulatory Molecules and Secmentioning

confidence: 99%

Section: Adenoviral Transduction Of Immature and Mature Dcsmentioning

confidence: 99%

Modulation of viability and maturation of human monocyte‐derived dendritic cells by oncolytic adenoviruses

Schierer

Hesse

Müller

et al. 2007

Intl Journal of Cancer

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“…When the donors harbored an anti-CAV-2 cellular response, it was on the average 10-fold lower than the response to hAdV serotype 5 (hAdV-5). Finally, in contrast to hAdV-5-based vectors, CAV-2 vectors poorly transduce or mature human dendritic cells or activate the complement cascade (37,40), both of which play pivotal roles in orchestrating and bridging innate, adaptive, and memory immune responses. These findings suggest that CAV-2 vectors may have specific clinical advantages, especially in terms of safety (39).…”

mentioning

confidence: 99%

Three-Dimensional Structure of Canine Adenovirus Serotype 2 Capsid

Schoehn

Bakkouri

Fabry

et al. 2008

J Virol

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There are more than 100 known adenovirus (AdV) serotypes, including 50 human serotypes. Because AdV-induced disease is relatively species specific, vectors derived from nonhuman serotypes may have wider clinical potential based, in part, on the lack of ubiquitous memory immunity. Whereas a few of the human serotype capsids have been studied at the structural level, none of the nonhuman serotypes has been analyzed. The basis laid by the analysis of human AdV (hAdV) has allowed us to determine and compare the threedimensional structure of the capsid of canine serotype 2 (CAV-2) to that of hAdV serotype 5 (hAdV-5). We show that CAV-2 capsid has a smoother structure than the human serotypes. Many of the external loops found in the hAdV-5 penton base and the hexon, against which the antibody response is directed, are shorter or absent in CAV-2. On the other hand, the CAV-2 fiber appears to be more complex, with two bends in the shaft. An interesting difference between the human and canine viruses is that the C-terminal part of protein IX is in a different position, making an antenna sticking out of the CAV-2 capsid. The comparison between the two viruses allows the identification of sites that should be easy to modify on the CAV-2 capsid for altering tissue tropism or other biological activities.

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“…Two E1/E3-deleted Ad5 vectors (Ad␤gal and AdGFP) were used in this study and were previously described (30). Briefly, Ad␤gal harbors a lacZ expression cassette and was used to stimulate Ad-specific T cells and for in vitro HIV infection (6 ϫ 10 9 physical particles [pp]/ml).…”

Section: Methodsmentioning

confidence: 99%

DNA/NYVAC Vaccine Regimen Induces HIV-Specific CD4 and CD8 T-Cell Responses in Intestinal Mucosa

Perreau

Welles

Harari

et al. 2011

J Virol

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In the present study, we have investigated the anatomic distribution in blood and gut mucosal tissues of memory poxvirus-specific CD4 and CD8 T cells in subjects vaccinated with smallpox and compared it with vector (NYVAC)-specific and HIV insert-specific T-cell responses induced by an experimental DNA-C/ NYVAC-C vaccine regimen. Smallpox-specific CD4 T-cell responses were present in the blood of 52% of the subjects studied, while smallpox-specific CD8 T cells were rarely detected (12%). With one exception, smallpoxspecific T cells were not measurable in gut tissues. Interestingly, NYVAC vector-specific and HIV-specific CD4 and CD8 T-cell responses were detected in almost 100% of the subjects immunized with DNA-C/NYVAC-C in blood and gut tissues. The large majority (83%) of NYVAC-specific CD4 T cells expressed ␣4␤7 integrins and the HIV coreceptor CCR5. These results demonstrate that the experimental DNA-C/NYVAC-C HIV vaccine regimen induces the homing of potentially protective HIV-specific CD4 and CD8 T cells in the gut, the port of entry of HIV and one of the major sites for HIV spreading and the depletion of CD4 T cells.

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Contrasting Effects of Human, Canine, and Hybrid Adenovirus Vectors on the Phenotypical and Functional Maturation of Human Dendritic Cells: Implications for Clinical Efficacy

Cited by 52 publications

References 90 publications

Modulation of viability and maturation of human monocyte‐derived dendritic cells by oncolytic adenoviruses

Modulation of viability and maturation of human monocyte‐derived dendritic cells by oncolytic adenoviruses

Three-Dimensional Structure of Canine Adenovirus Serotype 2 Capsid

DNA/NYVAC Vaccine Regimen Induces HIV-Specific CD4 and CD8 T-Cell Responses in Intestinal Mucosa

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