A5022723078- Virus-based gene therapy research
- RNA Interference and Gene Delivery
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- CRISPR and Genetic Engineering
- Glioma Diagnosis and Treatment
- Herpesvirus Infections and Treatments
- Viral Infectious Diseases and Gene Expression in Insects
- Neuroinflammation and Neurodegeneration Mechanisms
- Cancer Research and Treatments
- interferon and immune responses
- RNA modifications and cancer
- Animal Disease Management and Epidemiology
- T-cell and Retrovirus Studies
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Cancer Immunotherapy and Biomarkers
- Neuroscience and Neuropharmacology Research
- Viral gastroenteritis research and epidemiology
- Toxin Mechanisms and Immunotoxins
- RNA regulation and disease
- Monoclonal and Polyclonal Antibodies Research
- Influenza Virus Research Studies
- Vector-Borne Animal Diseases
- Pain Mechanisms and Treatments
Consejo Nacional de Investigaciones Científicas y Técnicas
2013-2024
National Agricultural Technology Institute
1999-2024
Centro Científico Tecnológico - San Juan
2017-2024
Cedars-Sinai Medical Center
2006-2023
University of California, Los Angeles
2004-2023
Fundación Instituto Leloir
2013-2018
Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria
2017
University of Michigan
2013-2014
Johns Hopkins Medicine
2008
Baylor College of Medicine
2005-2008
REVIEW article Front. Cell. Neurosci., 29 April 2013Sec. Non-Neuronal Cells Volume 7 - 2013 | https://doi.org/10.3389/fncel.2013.00053
Abstract In spite of preclinical efficacy and recent randomized, controlled studies with adenoviral vectors expressing herpes simplex virus-1 thymidine kinase (HSV1-TK) showing statistically significant increases in survival, most clinical trials using single therapies have failed to provide major therapeutic breakthroughs. Because glioma is a disease dismal prognosis rapid progression, it an attractive target for gene therapy. Preclinical models microscopic brain tumor (e.g., ≤0.3 mm3) may...
We have demonstrated that modifying the tumor microenvironment through intratumoral administration of adenoviral vectors (Ad) encoding conditional cytotoxic molecule, i.e., HSV1-TK and immune-stimulatory cytokine, fms-like tyrosine kinase 3 ligand (Flt3L) leads to T-cell-dependent regression in rodent models glioblastoma. investigated role B cells during immune-mediated glioblastoma multiforme regression. Although treatment with Ad-TK+Ad-Flt3L induced 60% wild-type (WT) mice, it completely...
Abstract Purpose: In preparation for a phase I clinical trial using combined cytotoxic/immunotherapeutic strategy with adenoviruses (Ad) expressing Flt3L (Ad-Flt3L) and thymidine kinase (Ad-TK) to treat glioblastoma (GBM), we tested the hypothesis that Ad-TK+GCV would be optimal tumor-killing agent in relation efficacy safety when compared other proapoptotic approaches. Experimental Design: The neurotoxicity of was Ads encoding cytokines [tumor necrosis factor-α, tumor factor–related...
Restricting the cytotoxicity of anticancer agents by targeting receptors exclusively expressed on tumor cells is critical when treating infiltrative brain tumors such as glioblastoma multiforme (GBM). GBMs express an IL-13 receptor (IL13Rα2) that differs from physiological IL4R/IL13R receptor. We developed a regulatable adenoviral vector (Ad.mhIL-4.TRE.mhIL-13-PE) encoding mutated human fused to Pseudomonas exotoxin (mhIL-13-PE) specifically binds IL13Rα2 provide sustained expression,...
The main challenge of gene therapy is to provide long-term, efficient transgene expression. Long-term expression from first generation adenoviral vectors (Advs) delivered the central nervous system (CNS) elicited in animals not previously exposed adenovirus (Ad). However, upon systemic immunization against Ad, a Adv abolished. High-capacity Advs (HC-Advs) sustained very long-term brain, even pre-immunized Ad. In this study, we tested hypothesis that HC-Adv brain would allow for expression,...
The most common primary brain tumor in adults is glioblastoma. These tumors are highly invasive and aggressive with a mean survival time of 15-18 months from diagnosis to death. Current treatment modalities unable significantly prolong patients diagnosed As such, glioma an attractive target for developing novel therapeutic approaches utilizing gene therapy. This review will examine the available preclinical models including xenograft, syngeneic genetic models. Several promising targets...
Following antigen recognition on target cells, effector T cells establish immunological synapses and secrete cytokines. It is thought that cytokines in one of two modes: either synaptically (i.e., toward antigenic cells) or multidirectionally, affecting a wider population cells. This paradigm predicts secreted such as IFN-γ will preferentially signal to contacted by the cell through an synapse. Despite its physiological significance, this prediction has never been tested. We developed...
Glioblastoma multiforme is an intracranial tumor that has very poor prognosis. Patients usually succumb to their disease 6 12 months after they are diagnosed despite aggressive treatment modalities. We tested the efficacy of a potent differentiation and proliferation factor for professional antigen-presenting dendritic cells (DCs), i.e., Flt3L, its potential role as novel therapy gliomas. investigated ability recombinant adenoviral vectors encoding human soluble Flt3L (hsFlt3L) improve...
The disseminated characteristics of human glioblastoma multiforme (GBM) make it a particularly difficult tumor to treat with long-term efficacy. Most preclinical models GBM involve treatment single mass. For therapeutic outcomes translate from the clinical setting, induction an antitumor response capable eliminating multifocal disease is essential. We tested hypothesis that expression Flt3L (human soluble FMS-like tyrosine kinase 3 ligand) and TK (herpes simplex virus type 1-thymidine...
Recombinant adenovirus vectors are attractive vehicles to deliver genes into the brain for purposes of neurobiological research and gene therapy neurological diseases. This unit provides a comprehensive set protocols vector-mediated transfer brain, including introduction vector by stereotaxic injection preparation processing tissue evaluation transfer. The potential side-effects administering discussed in detail. also evaluating these (e.g., demyelination, inflammation, cytotoxicity, etc.)....
Background Our goal is to use gene therapy alleviate pain by targeting glial cells. In an animal model of facial we tested the effect transfecting glutamic acid decarboxylase (GAD) into satellite cells (SGCs) trigeminal ganglion using a serotype 5 adenovector with high tropisms for We postulated that GABA produced from expression GAD would reduce behavior acting on receptors neurons within ganglion. Results Injection adenoviral vectors (AdGAD65) directly leads sustained GAD65 isoform over 4...
Bovine herpesvirus type 1 (BoHV-1) is the causative agent of respiratory and genital tract infections; causing a high economic loss in all continents. Use marker vaccines IBR eradication programs widely accepted since it allows for protection animals against disease while adding possibility differentiating vaccinated from infected animals. The aim present study was development evaluation safety efficacy glycoprotein E-deleted (gE-) BoHV-1 vaccine strain (BoHV-1ΔgEβgal) generated by...
To analyze the in vivo structure of antigen-specific immunological synapses during an effective immune response, we established brain tumors expressing surrogate tumor antigen ovalbumin and labeled anti-glioma T cells using specific tetramers. Using these techniques, determined that a significant number were localized to surrounding tissue large percentage could be induced express IFNgamma when exposed ovalbumin-derived peptide epitope SIINFEKL. Detailed morphological analysis immunoreactive...
Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor in humans. Systemic immunity against gene therapy vectors has been shown to hamper therapeutic efficacy; however, helper-dependent high-capacity adenovirus (HC-Ad) elicit sustained transgene expression, even presence of systemic anti-adenoviral immunity. We engineered HC-Ads encoding conditional cytotoxic herpes simplex type 1 thymidine kinase (TK) immunostimulatory cytokine fms-like tyrosine ligand 3...
Glioblastoma multiforme is the most common primary brain cancer in adults. Chemotherapy with temozolomide (TMZ) significantly prolongs survival of patients glioblastoma multiforme. However, three-year still approximately 5%. Herein, we combined intratumoral administration an adenoviral vector expressing Flt3L (Ad-Flt3L) systemic to assess its impact on therapeutic efficacy.Wild-type or immunodeficient mice bearing intracranial metastatic melanoma were treated injection Ad-Flt3L alone...
This study analysed sera from 390 llamas ( Lama glama ) nine farms located in three different Argentine provinces: Buenos Aires, Cordoba and Jujuy. The samples were tested for antibodies against 8 virus known to infect cattle: bovine herpesvirus type 1 (BHV‐1), viral diarrhea (BVDV), adenovirus (BAdV III), enterovirus (BEV), rotavirus (BRV), bluetongue (BTV), leukaemia (BLV), foot‐and‐mouth (FMDV) by conventional methods such as seroneutralization, immunoperoxidase staining, agar gel...
Expression of the immune-stimulatory molecule Fms-like tyrosine kinase 3 ligand (Flt3L) and conditional cytotoxic enzyme herpes simplex virus type 1 thymidine (HSV1-TK) provides long-term immune-mediated survival large glioblastoma multiforme (GBM) models in rodents. A limitation for predictive testing novel antiglioma therapies has been lack a glioma model animal. Dogs bearing spontaneous GBM may constitute an attractive large-animal GBM, which so far remained underappreciated. In...
Astrocytes usually respond to trauma, stroke, or neurodegeneration by undergoing cellular hypertrophy, yet, their response a specific immune attack T cells is poorly understood. Effector establish contacts with target cells, known as immunological synapses, during clearance of virally infected from the brain. Immunological synapses mediate intercellular communication between and both in vitro vivo. How astrocytes formation established effector unknown.Herein we demonstrate that, consequence...
ABSTRACT Glioblastoma multiforme (GBM) is a deadly primary brain tumor. Conditional cytotoxic/immune-stimulatory gene therapy (Ad-TK and Ad-Flt3L) elicits tumor regression immunological memory in rodent GBM models. Since the majority of patients enrolled clinical trials would exhibit adenovirus immunity, which could curtail transgene expression therapeutic efficacy, we used high-capacity vectors (HC-Ads) as delivery platform. Herein, describe for first time novel bicistronic HC-Ad driving...
Influenza viruses constitute a major threat to human health globally. The viral surface glycoprotein hemagglutinin (HA) is the immunodominant antigen, contains site for binding cellular receptor (RBS), and it target of neutralizing antibody responses post-infection. We developed llama-derived single chain fragments (VHHs) specific type A influenza virus. Four VHHs were identified further characterized. VHH D81 bound residues in proximity C-terminal region HA1 H1 H5 subtypes, showed weak...