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Adenoviral Vector Transduction of Dendritic Cells is Inhibited by Plasma from Cancer Patients

ABSTRACT: Adenoviral Vector Transduction of Dendritic Cells is Inhibited by Plasma from Cancer Patients

PROVIDER: PRJNA422874 | ENA |

REPOSITORIES: ENA

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Adenoviral Vector Transduction of Dendritic Cells is Inhibited by Plasma from Cancer Patients

Project description:Background: Pooled AB serum is often used as a media supplement for cell culture but it has the potential to transmit infectious diseases. To avoid this risk, we used autologous plasma as a media supplement for manufacturing dendritic cells (DCs) for cancer immunotherapy. We noticed inconsistences in the DCs and investigated its nature and cause. Methods: adHER2/neu DCs for 21 patients were manufactured from autologous peripheral blood monocytes which were treated with G-CSF and IL-4 for 3 days, transduced with Ad5f35HER2ECTM and then treated with lipopolysaccharide and IFN- for one day. The cells were cultured in RPMI-1640 supplemented with either 10% heat inactivated autologous or AB plasma. Results: Twenty-eight adHER2/neu DCs were manufactured for 21 patients using autologous plasma and 68 were manufactured for 20 of those patients using AB plasma. The expression of HER2/neu was less for DCs manufactured with autologous plasma (70.3±33.3% vs 86.1±22.8%, p<0.01). Manufacturing adHER2/neu DCs using monocytes from 3 healthy subjects and plasma from one patient with low HER2/neu expression (18%) resulted in low HER2/neu expression by all three DCs (13%, 16% and 23%). Analysis of the levels of 1322 proteins in 8 plasma samples associated with low HER2/neu expression and in 12 associated with high HER2/neu expression revealed that the levels of 14 predicted HER2/neu transduction efficiency. Conclusion: The manufacture of adHER2/neu DC using autologous plasma as a media supplement resulted in inconsistent HER2/neu expression. It is likely that variability in the levels of multiple proteins in autologous plasma contributed to low HER2/neu expression.

2018-12-17 | GSE108225 | GEO

Plasma from some cancer patients inhibits adenoviral Ad5f35 vector transduction of dendritic cells.

Project description:BACKGROUND:Pooled AB serum is often used as a media supplement for cell culture but it has the potential to transmit infectious diseases. To avoid this risk, we used autologous plasma as a media supplement for manufacturing dendritic cells (DCs) for cancer immunotherapy. We noticed inconsistencies in the DCs and investigated their nature and cause. METHODS:Adenovirus human epidural growth factor receptor 2 (adHER2/neu) DCs for 21 patients were manufactured from autologous peripheral blood monocytes that were treated with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4 for 3 days, transduced with Ad5f35HER2ECTM and then treated with lipopolysaccharide and interferon (IFN)-? for 1 day. The cells were cultured in RPMI-1640 supplemented with either 10% heat inactivated autologous or AB plasma. RESULTS:Twenty-eight adHER2/neu DCs were manufactured for 21 patients using autologous plasma and 68 were manufactured for 20 of those patients using AB plasma. The expression of human epidural growth factor receptor 2 (HER2/neu) was less for DCs manufactured with autologous plasma (70.3?±?33.3% versus 86.1?±?22.8%; P?<0.01). Manufacturing adHER2/neu DCs using monocytes from three healthy subjects and plasma from one patient with low HER2/neu expression (18%) resulted in low HER2/neu expression by all three DCs (13%, 16% and 23%). Analysis of the levels of 1322 proteins in eight plasma samples associated with low HER2/neu expression and in 12 associated with high HER2/neu expression revealed that the levels of 14 predicted HER2/neu transduction efficiency. CONCLUSION:The manufacture of adHER2/neu DC using autologous plasma as a media supplement resulted in inconsistent HER2/neu expression. It is likely that variability in the levels of multiple proteins in autologous plasma contributed to low HER2/neu expression.

| S-EPMC6014594 | biostudies-literature

Expression analysis of human ex vivo cultivated urothelial carcinoma samples transduced with a trivalent adenoviral vector (Im02) for activation of the immune tumor microenvironment.

Project description:The trivalent adenoviral vector Im02 encodes the cDNAs for human 4-1BBL, IL-12 and IL-2. This vector was designed to change the immune tumor microenvironment. In this study we investigated the immune stimulating effect of Im02 on human primary urothelial cancer specimens or normal urothelium by microarray RNA expression analysis. The tissues were transduced with Im02 or an adenoviral vector without expression cassette and were further cultivated for six days. Samples without transduction and cultivation were analysed to determine the status of the microenvironment.

2021-01-01 | E-MTAB-7623 | biostudies-arrayexpress

Expression analysis of human ex vivo cultivated urothelial carcinoma samples transduced with a trivalent adenoviral vector (Im02) for activation of the immune tumor microenvironment.

Project description:The trivalent adenoviral vector Im02 encodes the cDNAs for human 4-1BBL, IL-12 and IL-2. This vector was designed to change the immune tumor microenvironment. In this study we investigated the immune stimulating effect of Im02 on human primary urothelial cancer specimens or normal urothelium by RNASeq expression analysis. The tissues were transduced with Im02 or an adenoviral vector without expression cassette and were further cultivated for six days. Samples without transduction and cultivation were analysed to determine the status of the microenvironment.

2020-06-18 | E-MTAB-7659 | biostudies-arrayexpress

Transcription profiling of human HepG2 cells treated with UVC (254 nm) for 30 seconds and transduced with Adenoviral vector carrying the Hepatitis B Virus HBx gene vs Adenoviral vector control under UV treatment

Project description:Transcriptional profiling of HepG2 cells treated with UVC (254 nm) for 30 seconds and transduced with Adenoviral vector carrying the Hepatitis B Virus HBx gene vs Adenoviral vector control under UV treatment Experiment Overall Design: One-condition experiment, AdHBx (experimental) UV vs AdEasy (vector control) UV. HepG2 cells were infected with either recombinant HBx adenoviruses (AdHBx) or control adenoviruses (AdEasy). Seventy-two hours later, infected cells were exposed for 30 seconds to UVC (254 nm) irradiation with a germicidal lamp calibrated to deliver 8 or 16 J/m2. Cells were then harvested for either ChIP-chip profiling or expression microarray profiling

2008-10-21 | E-GEOD-11064 | biostudies-arrayexpress

Proof of Gene Doping in a Mouse Model with a Human Erythropoietin Gene Transferred Using an Adenoviral Vector

Project description:Gene doping model by hEPO (human erythropoietin) and adenoviral vector was established in the study. This study revealed that the gene expression profile in whole blood on the gene doping model significantly altered, which may be a new marker of hEPO-gene doping

2021-08-11 | GSE178336 | GEO

Adenoviral vector vaccination induces a conserved program of CD8+ T cell memory differentiation in mouse and man

Project description:Following exposure to vaccines, antigen-specific CD8+ T-cell responses develop as long-term memory pools. Novel vaccine strategies based on adenoviral vectors, e.g. those developed for HCV, are able to induce and sustain substantial CD8+ T-cell populations. How such populations evolve following vaccination remains to be defined at a transcriptional level. We addressed the transcriptional regulation of divergent CD8+ T-cell memory pools induced by an adenoviral vector encoding a model antigen (beta-galactosidase). We observe transcriptional profiles that mimic those following infection with persistent pathogens, murine and human cytomegalovirus (CMV). Key transcriptional hallmarks include up-regulation of homing receptors, and anti-apoptotic pathways, driven by conserved networks of transcription factors, including T-bet (TBX21). In humans, a novel adenovirus vaccine induced similar CMV-like phenotypes and underlying transcription factor regulation. These data clarify the core features of CD8+ T-cell memory following vaccination with adenovirus vectors and indicate a conserved pathway for memory development shared with persistent herpesviruses.

2015-09-23 | GSE73314 | GEO

Adenoviral Transduction of ARL11 in NHU-hTERT cells

Project description:Analyses of the whole genome mRNA gene expression profiling performed on ARL11-transducted normal urothelium cells. The results revealed that TP53, RB1 and CDKN2A pathways were activated and the E2F1 and MYC pathways were inhibited in cells expressing ARL11. ARL11-transducted cells also inhibited RAS pathway activation.

2024-07-17 | GSE49021 | GEO

Expression-analysis of human peripheral blood mononuclear cells (PBMC) cocultivated with RT-4 cells transduced with a trivalent adenoviral vector (Im02) for expression of 4-1BBL, IL-12 and IL-2

Project description:The trivalent adenoviral vector Im02 encodes the cDNAs for human 4-1BBL, IL-12 and IL-2. This vector was designed to change the immune tumor microenvironment. At the outset, we investigated the immune stimulating effect of Im02 transduced urothelial cancer cells (RT-4). Human PBMCs of a healthy donor were cocultured with these cells in a time series experiment. An adenoviral vector without expression cassette and cultivation without a vector were applied as control.

2021-01-01 | E-MTAB-7615 | biostudies-arrayexpress

Adenoviral vector vaccination induces a conserved program of CD8+ T cell memory differentiation in mouse and man

2015-09-23 | E-GEOD-73314 | biostudies-arrayexpress

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