A5061304621- Virus-based gene therapy research
- Viral gastroenteritis research and epidemiology
- Cancer Research and Treatments
- Animal Virus Infections Studies
- CAR-T cell therapy research
- Cell death mechanisms and regulation
- RNA Interference and Gene Delivery
- Infant Nutrition and Health
- MicroRNA in disease regulation
- Immune Response and Inflammation
- Biomedical Ethics and Regulation
- interferon and immune responses
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- CRISPR and Genetic Engineering
- Influenza Virus Research Studies
- Herpesvirus Infections and Treatments
- Viral Infectious Diseases and Gene Expression in Insects
- Pluripotent Stem Cells Research
Leiden University Medical Center
2015-2025
Utrecht University
2020
Significance Granzymes are serine proteases released by cytotoxic lymphocytes and induce cell death in virus-infected cells tumor cells. However, granzymes also exist extracellularly the blood circulation of patients with autoimmune diseases infections may contribute to inflammation. Here, we show that human granzyme K (GrK) binds Gram-negative bacteria lipopolysaccharide (LPS), a bacterial wall component. Our data indicate GrK lowers threshold for monocyte activation LPS, synergistically...
Due to the minimal survival benefits of existing therapies for pediatric diffuse midline glioma (DMG) patients, new therapeutic modalities are being investigated. Immunotherapies such as CAR-T cells and oncolytic viruses (OVs) part these efforts, evidenced by increasing number clinical trials. αβ T engineered with a high-affinity γ9δ2 T-cell receptor (TEGs) immune designed target metabolic changes in malignant or virally infected via BTN2A1 BTN3A. Because expression BTN3A can be altered...
Despite decades of research, the prognosis high-grade pediatric brain tumors (PBTs) remains dismal; however, recent cases favorable clinical responses were documented in trials using oncolytic viruses (OVs). In current study, we employed four different species OVs: adenovirus Delta24-RGD, herpes simplex virus rQNestin34.5v1, reovirus R124, and non-virulent Newcastle disease rNDV-F0-GFP against three entities PBTs (high-grade gliomas, atypical teratoid/rhabdoid tumors, ependymomas) to...
Abstract Avian infectious bronchitis virus (IBV) is a coronavirus with great economic impact on the poultry industry, causing an acute and highly contagious disease in chickens that primarily affects respiratory reproductive systems. The cellular regulation of IBV pathogenesis host immune responses involved remain to be fully elucidated. MicroRNAs (miRNAs) have emerged as class crucial regulators numerous processes, including viral infections. Here, we employed high-throughput sequencing...
Gastrointestinal (GI) cancers are characterized by extensive tumor stroma that both promotes progression and acts as a physical barrier for adjacent cells, limiting the effect of current treatment modalities. Oncolytic virotherapy is currently investigated in clinical trials novel therapeutic agent different malignancies GI tract, but it largely unknown whether these viruses can also target stroma. Here, we tropism two commonly studied OVs, adenovirus reovirus, towards primary fibroblasts...
Infection of chicken coronavirus infectious bronchitis virus (IBV) is initiated by binding the viral heavily N-glycosylated attachment protein spike to alpha-2,3-linked sialic acid receptor Neu5Ac. Previously, we have shown that N-glycosylation recombinantly expressed domain (RBD) IBV-M41 critical importance for trachea tissue. Here investigated role RBD on specificity and replication in context particle. Using our reverse genetics system were able generate recombinant IBVs nine-out-of-ten...
Mammalian reovirus is a double-stranded RNA virus that selectively infects and lyses transformed cells, making it an attractive oncolytic agent. Despite clinical evidence for anti-tumor activity, its efficacy as stand-alone therapy remains to be improved. The success of future trials can greatly influenced by the identification regulation cellular pathways are important replication oncolysis. Here, we demonstrate induces autophagy in several cell lines, evident from formation Atg5-Atg12...
The use of human adenoviruses (hAds) as oncolytic agents has demonstrated considerable potential. However, their efficacy in clinical studies is generally moderate and often varies between patients. This may, part, be attributable to variable pre-existing neutralizing immunity patients, which can impact the antitumor lead response heterogeneity. Our aim was isolate new Ads for development vectors with low prevalence population. To this end, we isolated a collection nonhuman primate (nhp)...
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy which shows unparalleled therapeutic resistance due to its genetic and cellular heterogeneity, dense stromal tissue, immune-suppressive tumour microenvironment. Oncolytic virotherapy has emerged as new treatment modality uses tumour-specific viruses eliminate cancerous cells. Non-human primate adenoviruses of the human adenovirus B (HAdV-B) species have demonstrated considerable lytic potential in cancer cells well...
Abstract Pancreatic tumors display an abundance of cancer-associated fibroblasts (CAFs), which negatively affect prognosis and therapy response. Oncolytic virotherapy exploits viruses that preferentially lyse epithelial cancer cells as opposed to normal cells. Interestingly, we have observed oncolytic reoviruses are able infect CAFs, in addition Targeting cells, could be advantageous increase effectiveness. It serve a conduit for viral spread simultaneously disrupt the desmoplastic barrier...
Reoviruses are used as oncolytic viruses to destroy tumor cells. The concomitant induction of anti-tumor immune responses enhances the efficacy therapy in tumors with low amounts infiltrates before treatment. reoviruses should provoke immunogenic cell death (ICD) stimulate a cell-directed response. Necroptosis is considered major form ICD, and involves receptor-interacting protein kinase 1 (RIPK1), RIPK3 phosphorylation mixed-lineage domain-like (MLKL). This leads membrane disintegration...
The adenoviruses (AdVs) isolated from humans are taxonomically grouped in seven different species the Mastadenovirus genus (HAdV-A through G). AdVs apes often included one of human AdV species. Here we describe sequence analyses ten new that related to HAdV-C and were healthy western lowland gorillas, bonobos, chimpanzees, orangutans kept Dutch zoos. We analyzed these viruses compared their genome sequences those human- ape-derived NCBI GenBank database. Our data demonstrated clustering...