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Adenovirus clinical trials

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NCT ID: NCT03325517 Not yet recruiting - Adenovirus Clinical Trials

Effect of Adenovirus E1A Oncogene on DNA Replication Dynamics

Start date: November 1, 2017
Phase: N/A
Study type: Observational

BACKGROUND: The 243 amino acid E1A encoded by the left end of the human adenovirus (Ad) type 2 or 5 genome has been studied in various contexts including as a model cooperating oncoprotein , an apoptosis inducing protein, and as a therapeutic oncolytic protein. All of these properties are associated with its capacity to rapidly induce S phase in a variety of cells. E1A orchestrates most of these effects by interacting with an array of chromatin remodeling complexes, including the Rb family proteins, and the HAT proteins p300 and CBP. The Myst family protein HBO1 (Myst2, KAT7) is a histone acetyl transferase that plays a major role in replication initiation and also contributes to DNA re-replication. HBO1 directly interacts with Cdt1 and functions as a coactivator of Cdt1 in replication initiation. It also associates with replication origin and stimulates origin activation by acetylating H4 K5, K8, and K12. Overexpression of HBO1 induces DNA re-replication. SPECIFIC AIM OF THE STUDY: The Specific Aim of this study is to determine whether or not the stimulation of HBO1 activity by E1A plays a role in deregulated DNA replication, and if it does, to determine the mechanism. 1. Using standard assays the investigators will determine whether E1A binds to HBO1 to induce its HAT activity 2. The investigators will determine whether E1A stimulation of HAT activity of HBO1 contributes to DNA re-replication. RESEARCH DESIGN AND METHODS: First, the investigators will determine whether E1A associates with replication origins and whether this association requires HBO1. The investigators will use the MCM4 origin which maps in the intergenic region between PRKDC and (Protein Kinase, DNA-Activated, Catalytic Polypeptide) and MCM4 genes. The investigators will transfect U2OS cells with plasmids expressing relevant proteins then determine their occupancy in origin sequences using ChIP assays. Plasmids expressing epitope tagged WT HBO1 or mutant derivatives along with plasmids expressing WT or mutant E1A proteins will be expressed in U2OS cells, then occupancy of these proteins on origin regions will be quantified using antibodies as appropriate. Typically in these experiments, using relevant antibodies, ChIP assays are performed with primer pairs encompassing origin regions and also regions that are far from origin. Occupancy of initiation factors are increased several fold in the origin region as compared to that of 2KB upstream or downstream regions. Loading of MCM complex along with Cdt1 onto the origins is an indication that initiation of replication occurs in that origin and usually assayed in ChIP-re-ChIP assays as follows: First, loading of HBO1 to the origins will be confirmed using epitope specific antibodies in the first ChIP. The anti-HBO1 precipitates will be re-ChIPed with anti-MCM3 antibodies. Loading of MCM3 helicase to origins occurs after Cdt1 binding and depends on HBO1 HAT activity. Normal amounts of MCM3 will be detected after re-ChIP-ing in E1A+ control samples. If reduced amount of MCM3 is recovered in reChIP assays when mutant E1A or HBO1 mutant (e.g. HBO1 G435A) is used, it would indicate that stimulation of HAT activity by E1A is critical for maximal origin activity in E1A+ cells. This type of assay has considerable flexibility in that mutant proteins can be rapidly assayed. This ChIP-reChiP assays will repeated in different combinations to determine the E1A loading. These results will be extended to virus infection assays. G1 specific cells isolated by drug treatment will be infected with Ad vectors expressing epitope tagged proteins as appropriate. Association of E1A and HBO1 and their mutant derivatives will be determined. This assay will allow us to confirm the effect of E1A stimulated HAT activity in origin firing and study the effects of E1A on origin firing, if any, other than increasing the HAT activity of HBO1.

NCT ID: NCT03266627 Recruiting - Clinical trials for Primary Immune Deficiency Disorder

Adenovirus-specific Cytotoxic T-lymphocytes for Refractory Adenovirus Infection

Start date: November 1, 2018
Phase: Phase 2
Study type: Interventional

Related donor Adenovirus (ADV) specific cytotoxic T cells (CTLs) manufactured with the Miltenyi CliniMACS Prodigy Cytokine Capture System will be administered intravenously in in children, adolescents and young adults with refractory ADV infection post Allogeneic Hematopoietic Stem Cell Transplantation (AlloHSCT), with primary immunodeficiencies (PID) or post solid organ transplant. Funding Source: FDA OOPD

NCT ID: NCT02984280 Completed - Clinical trials for Cardiovascular Diseases

Specific Respiratory Infections as Triggers of Acute Medical Events

Start date: September 2016
Phase: N/A
Study type: Observational

This study will investigate whether there is a population-level association between circulating respiratory viruses and NHS hospital admissions for acute vascular events using data from national infection surveillance and Hospital Episode Statistics.

NCT ID: NCT02779439 Recruiting - CMV Infection Clinical Trials

Partially HLA-matched Third Party Antigen Specific T-cells for Infection Post-stem Cell or Solid Organ Transplantation

R3ACT
Start date: January 2013
Phase: Phase 1
Study type: Interventional

To assess the safety and biological efficacy of therapeutically administered most closely HLA-matched third party donor-derived specific cytotoxic T lymphocytes (CTLs) targeting cytomegalovirus (CMV) or Adenovirus (Adv) or Epstein Barr virus (EBV) or fungi including Aspergillus and Candida species for the treatment of viral infection following allogeneic blood or marrow stem cell or solid organ transplantation.

NCT ID: NCT02596997 No longer available - Adenovirus Clinical Trials

Expanded Access Protocol to Provide Brincidofovir for the Treatment of Serious Adenovirus Infection or Disease

Start date: n/a
Phase:
Study type: Expanded Access

Provide patients with serious AdV infection or disease access to treatment with BCV.

NCT ID: NCT02420080 Terminated - Adenovirus Clinical Trials

A Multicenter Study to Obtain Retrospective Data for Subjects Previously Diagnosed With Adenovirus Infection to Serve as Matched Historical Controls for Study CMX001-304

Start date: February 2015
Phase: N/A
Study type: Observational

The objective is data collection to determine background rates of adenovirus (AdV) progression and mortality in subjects with Adenovirus (AdV) infection and/or disease.

NCT ID: NCT02008812 Recruiting - Adenovirus Clinical Trials

Ad Sensor-based Real-time Diagnosis of Adenovirus

Start date: August 2011
Phase: N/A
Study type: Interventional

To develop a real-time diagnostic technique with Ad sensor for Adenovirus detection, the investigators conduct a prospective clinical study. In comparison with results from direct sequencing of Adenovirus, the investigators evaluate the performance of Ad sensor , including reproducibility, sensitivity, specificity, and cross-reaction. The potential factors which may interfere with the results would be investigated. With such technique, the investigators hope to make early diagnosis and give Adenovirus patients early treatment to reduce the complications and case-fatality rate.

NCT ID: NCT01945814 Active, not recruiting - CMV Clinical Trials

Allogeneic Multivirus - Directed Cytotoxic T Lymphocytes (CTL)

Start date: February 2014
Phase: Phase 1
Study type: Interventional

In this study, investigators are trying to see if infusion of T cells (called CTLs) will prevent or treat cytomegalovirus (CMV), Epstein Barr Virus (EBV) and adenovirus (AdV) reactivation or infection. Patients with blood cell cancer, other blood disease or a genetic disease may receive a stem cell transplant. After receiving transplant, they are at risk of infections until a new immune system to fight infections grows from the cord blood cells. In this study, investigators are trying to give special cells called T cells. These cells will try to fight viruses that can cause infection. Investigators will test to see if blood cells from donor that have been grown in a special way, can prevent patients from getting an infection. EBV, AdV and CMV are viruses that can cause serious life-threatening infections in patients who have weak immune systems after transplant. T lymphocytes can kill viral cells but normally there are not enough of them to kill all the virus infected cells after transplant. Some researcher have taken T cells from a person's blood, grown more of them in the laboratory and then given them back to the person during a viral infection after a bone marrow transplant. Some of these studies have shown a positive therapeutic effect in patients receiving the CTLs after a viral infection in the post-transplant period. Investigators will grow these cells from donor in the laboratory in a way that will train them to recognize and remove viruses when the T cells are given after a transplant. Since most donors have previously been infected with EBV, CMV, and adenovirus, investigators are able to use their T cells that remember these viruses to grow the CTLs. However, they now also have a new way of growing CTLs from donors who have not been infected with CMV.

NCT ID: NCT01600365 Not yet recruiting - Conjunctivitis Clinical Trials

Evaluate the Use of Ganciclovir Gel 0.3% for the Treatment of Conjunctivitis Caused by Adenovirus

Start date: May 2012
Phase: Phase 3
Study type: Interventional

The purpose of this study is to study the use of ganciclovir gel 0.3% for treatment of conjunctivitis caused by adenovirus.

NCT ID: NCT01584037 Withdrawn - Adenovirus Clinical Trials

Adenovirus Vaccine Pregnancy Registry

Start date: December 2011
Phase: N/A
Study type: Observational [Patient Registry]

The primary purpose of the Adenovirus Vaccine Pregnancy Registry is to prospectively collect data concerning: 1. Pregnant women exposed to Adenovirus Type 4 and Type 7 Vaccine, Live, Oral, 2. Potential confounding factors, and 3. The outcome of these pregnancies. The secondary purpose of the Adenovirus Vaccine Pregnancy Registry is to evaluate the frequency of birth defects in prospectively enrolled pregnant women. This Registry is also designed to detect any unusual patterns of birth defects.