View clinical trials related to Adenoviridae Infections.
Filter by:This phase I trial studies the side effects of allogeneic adenovirus-specific cytotoxic T lymphocytes (donor T cell therapy) and to see how well they work in treating patients with a weakened immune system (immunocompromised) and adenovirus-related disease. Allogeneic adenovirus-specific cytotoxic T lymphocytes are made from donated blood cells grown in the laboratory and are designed to kill viruses that can cause infections in immunocompromised patients with adenovirus-related disease.
The purpose of this study is to determine if it is possible to treat an infection with a cell-based immunotherapy (therapy that uses the patient's own immune system to treat the infection). This treatment is called adoptive T cell therapy. Another purpose is to learn about the side effects and toxicities of adoptive T cell therapy. Adoptive T cell therapy is an investigational (experimental) therapy that works by using the blood of a donor that has immunity against the virus. The donor cells are collected and then the cells, called T cells, that are capable of defending against the virus are selected out. These selected T cells are then infused back into the patient, to try to give the immune system the ability to fight the infection. Adoptive T cell therapy is experimental because it is not approved by the Food and Drug Administration (FDA).
This study was designed to assess the safety, overall tolerability, and antiviral activity of "short course" brincidofovir (BCV) therapy, as compared with current standard of care (SoC), for the treatment of adenovirus (AdV) infections in high-risk (i.e., T cell depleted) pediatric allogeneic hematopoietic cell transplant (HCT) recipients. A virologic response-driven approach to the duration of treatment was to be evaluated, in which subjects randomized to BCV therapy were to be treated until AdV viremia was confirmed as undetectable or until a maximum of 16 weeks of therapy, whichever occurred first. The formulation of BCV used in this study was oral tablet/suspension.
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.
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
PXVX0047 (Adenovirus Type 4 and Type 7 Vaccine [A549 Cells], Live, Oral) is an investigational vaccine in development for the indication of active immunization against adenovirus infection. The primary goals of this Phase 1 study are to evaluate safety, pharmacodynamics (viral shedding), and immunogenicity of PXVX0047.
Epstein Barr Virus (EBV) or Cytomegalovirus (CMV) infection results in significant morbidity and mortality in hematopoietic stem cell transplantation (HSCT) patients. HSCT patients often face opportunistic infections due to the immunosuppressive state during transplantation. Antimicrobial drugs are usually used for prophylactic purposes and for treatment after early detectable infections. Unfortunately, some patients develop resistance to such drug treatment. In addition to HSCT patient, immune compromised patient may also be victim to opportunistic infections. Many infections can be effectively managed by functional immune recovery. In this study, the safety and efficacy of microbial-specific cytotoxic T lymphocytes (CTLs) will be investigated.
The primary objective of this phase 1 trial is to determine the dose-dependent toxicity and maximum tolerated dose (MTD) of oncolytic adenovirus-mediated cytotoxic gene therapy in combination with SBRT in medically inoperable stage I/IIA (T1A - T2B) NSCLC. To accomplish this objective, 9 subjects will be enrolled in the study. We hypothesize that the combined treatment will demonstrate acceptable toxicity, and that it will be feasible to quantify adenovirus-mediated HSV-1 TK gene expression in the lung by PET. This phase 1 trial will lay the foundation for a follow-up phase 2 trial designed to examine efficacy.
Fourteen patients will be included for infusion of adenovirus-specific T-cells generated by a clinical grade IFN-γ based immunomagnetic isolation from a leukapheresis from their original donor or a haploidentical donor, in case of Umbilical cord blood transplantation, in the event of refractory ADV infection or disease.
Glioblastoma (GBM) and gliosarcoma (GS) are the most common and aggressive forms of malignant brain tumor in adults and can be resistant to conventional therapies. The purpose of this Phase II study is to evaluate how well a recurrent glioblastoma or gliosarcoma tumor responds to one injection of DNX-2401, a genetically modified oncolytic adenovirus, when delivered directly into the tumor followed by the administration of intravenous pembrolizumab (an immune checkpoint inhibitor) given every 3 weeks for up to 2 years or until disease progression. Funding Source-FDA OOPD