A5084723610- Virus-based gene therapy research
- CAR-T cell therapy research
- Cancer Research and Treatments
- RNA Interference and Gene Delivery
- Parvovirus B19 Infection Studies
- CRISPR and Genetic Engineering
- Viral Infections and Immunology Research
- Animal Virus Infections Studies
- Viral Infectious Diseases and Gene Expression in Insects
- Viral gastroenteritis research and epidemiology
- Immunotherapy and Immune Responses
- Neuroblastoma Research and Treatments
- Renal and related cancers
- Pancreatic and Hepatic Oncology Research
- Ultrasound and Hyperthermia Applications
- interferon and immune responses
- Herpesvirus Infections and Treatments
- Phagocytosis and Immune Regulation
- Adipokines, Inflammation, and Metabolic Diseases
- Transplantation: Methods and Outcomes
- Ubiquitin and proteasome pathways
- T-cell and B-cell Immunology
- Cardiovascular Effects of Exercise
- Cancer, Hypoxia, and Metabolism
- Ferroptosis and cancer prognosis
Heidelberg University
2014-2024
German Cancer Research Center
2015-2024
DKFZ-ZMBH Alliance
2006-2020
Inserm
2011
Kyushu University
2008
Johannes Gutenberg University Mainz
2008
Common features of parvovirus capsids are open pores at the fivefold symmetry axes that traverse virion shell. Upon limited heat treatment in vitro, can function as portals to externalize VP1/VP2 protein N-terminal sequences which harbor infection-relevant functional domains, such a phospholipase A(2) catalytic domain. Here we show adeno-associated virus type 2 (AAV2) also exposes its N termini vivo during infection, presumably endosomal compartment. This conformational change is influenced...
As a prerequisite for clinical application, we determined the long-term therapeutic effectiveness and safety of adeno-associated virus (AAV)-S100A1 gene therapy in preclinical large animal model heart failure. S100A1, positive inotropic regulator myocardial contractility, becomes depleted failing cardiomyocytes humans animals, myocardial-targeted S100A1 transfer rescues cardiac contractile function by restoring sarcoplasmic reticulum calcium (Ca(2+)) handling acutely chronically hearts small...
Abstract Background The treatment of patients with malignant brain tumors remains a major oncological problem. median survival glioblastoma multiforme (GBM), the most type, is only 15 months after initial diagnosis and even less tumor recurrence. Improvements standard including surgery radio-chemotherapy have not lead to improvements. Therefore, alternative therapeutics such as oncolytic viruses that specifically target destroy cancer cells are under investigation. Preclinical data...
Vectors based on recombinant adeno-associated virus 2 (AAV-2) are a promising tool for cardiac gene transfer. However, potential therapeutic applications need to consider the predominant transduction of liver once AAV-2 vectors enter systemic circulation. We therefore aimed increase efficiency and specificity vector delivery by combining transcriptional cell surface targeting.For analysis targeting, AAV were generated harboring luciferase reporter under control cytomegalovirus (CMV) promoter...
A recombinant adeno-associated virus serotype 2 Reference Standard Material (rAAV2 RSM) has been produced and characterized with the purpose of providing a reference standard for particle titer, vector genome infectious titer AAV2 gene transfer vectors. Production purification material were carried out by helper virus–free transient transfection chromatographic purification. The purified bulk was vialed, confirmed negative microbial contamination, then distributed characterization along...
Abstract Pancreatic carcinoma is a gastrointestinal malignancy with poor prognosis. Treatment gemcitabine, the most potent chemotherapeutic against this cancer up to date, not curative, and resistance may appear. Complementary treatment an oncolytic virus, such as rat parvovirus H-1PV, which infectious but nonpathogenic in humans, emerges innovative option. Purpose: To prove that combining gemcitabine H-1PV model of pancreatic reduce dosage toxic drug and/or improve overall anticancer...
Delivery of drugs and macromolecules to the central nervous system (CNS) is hindered by blood-brain barrier (BBB). Several approaches have been used overcome this hindrance facilitate treatment various CNS diseases. We now present results showing that chimeric adeno-associated virus 2/1 (AAV2/1) particles containing coding region for LacZ gene are efficiently delivered into rat brain upon intravenous (IV) administration after BBB opening focused ultrasound in presence vascular acoustic...
Gene therapy approaches using recombinant adeno-associated virus serotype 2 (rAAV2) and 8 (rAAV8) have achieved significant clinical benefits. The generation of rAAV Reference Standard Materials (RSM) is key to providing points reference for particle titer, vector genome infectious titer gene transfer vectors. Following the example rAAV2RSM, here we generated characterized a novel RSM based on 8. rAAV8RSM was produced transient transfection, purification density gradient ultracentrifugation....
AimsInducible gene targeting in mice using the Cre/LoxP system has become a valuable tool to analyse roles of specific genes adult heart. However, commonly used Myh6-MerCreMer requires time-consuming breeding schedules and is potentially associated with cardiac side effects, which may result transient dysfunction. The aim our study was establish rapid simple for inactivation conditional knockout by transfer Cre recombinase adeno-associated viral vectors serotype 9 (AAV9).
A temporal systems biology screen of premetastatic endothelial cells identified LRG1 as a therapeutic target for restricting metastases.
In mammals, proper storage and distribution of lipids in between tissues is essential for the maintenance energy homeostasis. Here, we show that tumour growth triggers hepatic metabolic dysfunction as part cancer cachectic phenotype, particularly by reduced very-low-density-lipoprotein (VLDL) secretion hypobetalipoproteinemia. As a molecular cachexia output pathway, levels transcription factor transforming beta 1-stimulated clone (TSC) 22 D4 were increased cachexia. Mimicking high TSC22D4...
Adeno-associated virus vectors are a powerful tool for gene transfer approaches. We have established simple and fast plasmid-based production system achieving high adeno-associated titers within 6 working days. The same procedure can be used all serotypes thus allows direct comparability of different serotypes. In this protocol we describe step-by-step that results in well-characterized suitable both vitro approaches preclinical studies.
Metastatic pancreatic cancer has a dismal prognosis, with mean six-month progression-free survival of approximately 50% and median about 11 months. Despite intensive research, only slight improvements clinical outcome could be achieved over the last decades. Hence, new innovative therapeutic strategies are urgently required. ParvOryx is drug product containing native parvovirus H-1 (H-1PV). Since H-1PV was shown to exert pronounced anti-neoplastic effects in pre-clinical models cancer,...
Abstract Purpose: To investigate the safety, clinical efficacy, virus pharmacokinetics, shedding, and immune response after administration of an oncolytic parvovirus (H-1PV, ParvOryx) to patients with metastatic pancreatic ductal adenocarcinoma (PDAC) refractory first-line therapy. Patients Methods: This is a noncontrolled, single-arm, open-label, dose-escalating, single-center trial. Seven PDAC at least one liver metastasis were included. ParvOryx was administered intravenously on 4...
Adeno-associated viruses (AAV) have been developed and evaluated as recombinant vectors for gene therapy in many preclinical studies, well clinical trials. However, only a few approaches used AAV (rAAV) to deliver vaccine antigens. We generated an rAAV encoding the major capsid protein L1 (L1h) from human papillomavirus type 16 (HPV16), aiming develop prophylactic against HPV16 infections, which are cause of cervical cancer women worldwide. A single dose rAAV5 L1h administered intranasally...
Cervical cancer is the second most common in women worldwide. Persistent high-risk human papillomavirus (HPV) infection has been identified as causative event for development of this type cancer. Recombinant adeno-associated viruses (rAAVs) are currently being developed and evaluated vaccine vector. In previous work, we demonstrated that rAAVs administered intranasally mice induced high titers long-lasting neutralizing antibodies against HPV 16 (HPV16). To extend approach to a more...
Oncolytic viruses represent novel tools for cancer treatment. Besides specifically killing cells (oncolysis), these agents also provide danger signals, prompting the immune system to eliminate virus-infected tumours. As a consequence of oncolytic events, innate and adaptive systems gain access tumour antigens, which result in cross-priming vaccination effects. Here aim was see whether we could enhance this adjuvant capacity by incorporating immunostimulatory CpG motifs into single-stranded...
Abstract Despite multimodal therapeutic concepts, advanced localized and high‐risk neuroblastoma remains a challenge with long‐term survival rate below 50%. Consequently, new modalities for the treatment of neuroblastoma, e.g ., oncolytic virotherapy are urgently required. H‐1PV is rodent parvovirus devoid relevant pathogenic effects in infected adult animals. In contrast, virus has properties particularly cytotoxic transformed or tumor‐derived cells various species including human origin....
Abstract Background Parvovirus H-1 (H-1PV) infects and lyses human tumor cells including melanoma, hepatoma, gastric, colorectal, cervix pancreatic cancers. We assessed whether the beneficial effects of chemotherapeutic agents or targeted could be combined with oncolytic immunostimmulatory properties H-1PV. Methods Using ex vivo models we evaluated biological immunological H-1PV-induced cell lysis alone in combination melanoma +/- characterized cytotoxic T-cells (CTL) HLA-A2-restricted...
Oncolytic viruses with their capacity to specifically replicate in and kill tumor cells emerged as a novel class of cancer therapeutics. Rat oncolytic parvovirus (H-1PV) was used treat different types preclinical settings lately successfully combined standard gemcitabine chemotherapy treating pancreatic ductal adenocarcinoma (PDAC) rats. Our previous work showed that the immune system particularly release interferon-gamma (IFNγ) seem mediate anticancer effect H-1PV model. Therefore, we...
In previous studies, we have shown that the apathogenic rat parvovirus H-1 (H-1PV) is capable to induce regression of advanced symptomatic and human gliomas in a model, when virus was injected tumor (intracranially) or intravenously. Infection with H-1PV did not provoke any pathology nontumor tissue. This study addresses question whether also intranasal application this oncolytic suitable sufficient for treating animal model.Rat (RG-2) (U87) glioma cells were grafted stereotactically brain...
ABSTRACT The rat parvovirus H-1PV is a promising anticancer agent given its oncosuppressive properties and the absence of known side effects in humans. replicates preferentially transformed cells, but virus can enter both normal cancer cells. Uptake by cells sequesters significant portion administered viral dose away from tumor target. Hence, targeting entry specifically to important increase efficacy parvovirus-based treatments. In this study, we first found that sialic acid plays key role...