A5055331012- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Virus-based gene therapy research
- CAR-T cell therapy research
- vaccines and immunoinformatics approaches
- Cancer Research and Treatments
- Monoclonal and Polyclonal Antibodies Research
- Cancer Immunotherapy and Biomarkers
- Circular RNAs in diseases
- Acute Myeloid Leukemia Research
- Immune cells in cancer
- HIV Research and Treatment
- interferon and immune responses
- Prenatal Screening and Diagnostics
- Viral gastroenteritis research and epidemiology
- Glycosylation and Glycoproteins Research
- Chronic Myeloid Leukemia Treatments
- Animal Virus Infections Studies
- RNA Interference and Gene Delivery
- Cancer-related molecular mechanisms research
- Epigenetics and DNA Methylation
- Circadian rhythm and melatonin
- Adrenal Hormones and Disorders
- Mycobacterium research and diagnosis
Ludwig-Maximilians-Universität München
2009-2024
Bavarian Nordic (Germany)
2017-2023
Universität für Weiterbildung Krems
2023
Research Institute of Molecular Pathology
2007
Medical University of Vienna
1986-2007
Abstract Virus-based vaccines and appropriate costimulation potently enhance antigen-specific T cell immunity against cancer. Here we report the use of recombinant modified vaccinia virus Ankara (rMVA) encoding costimulatory CD40L solid tumors. Therapeutic treatment with rMVA-CD40L-expressing tumor-associated antigens results in control established The expansion tumor-specific cytotoxic CD8 + cells is essential for therapeutic antitumor effects. Strikingly, rMVA-CD40L also induces strong...
The H3K9me3-specific histone methyltransferase Setdb1 impacts on transcriptional regulation by repressing both developmental genes and retrotransposons. How impaired retrotransposon silencing may lead to phenotypes is currently unclear. Here we show that loss of in pro-B cells completely abrogates B cell development. In cells, dispensable for lineage-inappropriate genes. Instead, detect strong derepression endogenous Murine Leukemia Virus (MLV) copies. This activation coincides with an...
According to the "two-step model," intrathymic generation of CD4⁺ regulatory T (T(reg)) cells segregates into a first, cell receptor (TCR)-driven phase and second, cytokine-dependent phase. The initial TCR stimulus gives rise CD25⁺Foxp3⁻ developmental intermediate. These precursors subsequently require cytokine signaling establish mature CD25⁺Foxp3⁺ T(reg) phenotype. In addition, costimulation via CD28/B7 (CD80/86) axis is important for repertoire normal size. Recent data suggest that CD28...
Significance Central tolerance can generate holes in the CD4 T cell repertoire or divert cells into Foxp3 + regulatory (T reg ) lineage. Little is known with regard to how these diametrically different fate decisions of autoreactive shape size and composition polyclonal cohorts antigen-specific cells. Here we generated inventories very rare naive versus tolerant identified receptors (TCRs) that were lost, whereas others mediated differentiation. The antigen responsiveness TCRs revealed a TCR...
The existence of lipid rafts and their importance for immunoreceptor signaling is highly debated. By non-invasive single molecule imaging, we analyzed the dynamics T-cell antigen receptor (TCR), raft-associated glycosylphosphatidylinositol (GPI) proteins CD48 CD59 major leukocyte phosphatase CD45 in living naive T lymphocytes. TCR triggering induced immobilization at different positions within interface. second GPI protein, CD59, did not co-immobilize indicating raft heterogeneity A novel...
Background Human cancers are extraordinarily heterogeneous in terms of tumor antigen expression, immune infiltration and composition. A common feature, however, is the host's inability to mount potent responses that prevent growth effectively. Often, naturally primed CD8+ T cells against solid tumors lack adequate stimulation efficient tissue penetration due an hostile microenvironment.Methods To address these shortcomings, we cloned tumor-associated antigens (TAA) immune-stimulatory ligand...
Background Peritoneal carcinomatosis is an advanced stage of cancer in which the disease has spread to peritoneal cavity. In order restore antitumor immunity subverted by tumor cells this location, we evaluated intraperitoneal administrations modified vaccinia virus Ankara (MVA) engineered express single-chain interleukin 12 (scIL-12) increase immune responses. Methods MVA encoding scIL-12 (MVA.scIL-12) was against models based on engraftment cells. CD8-mediated responses, elucidated...
Immunization with myelin components can elicit experimental autoimmune encephalomyelitis (EAE). EAE susceptibility varies between mouse strains, depending on the antigen employed. BL/6 mice are largely resistant to induction proteolipid protein (PLP), probably a reflection of antigen-specific tolerance. However, extent and mechanism(s) tolerance PLP remain unclear. Here, we identified three epitopes in PLP-deficient mice. PLP-sufficient did not respond against two these, whereas was "leaky"...
Recombinant-modified vaccinia virus Ankara (rMVA) is known to elicit potent antitumor immune responses in preclinical models due its inherent ability activate the innate system and activation of adaptive mediated by expression tumor antigens costimulus-providing molecules, such as CD40L CD137L. Here, we evaluated different rMVA vectors peritoneal carcinomatosis (ID8.OVA-Vegf/GFP MC38). We compared expressing a antigen (OVA or gp70) either alone co-expressed with or/and In tumor-free mice,...
Abstract The induction of antiviral innate immunity by systemic immunization with live virus can be employed to positively impact the response therapeutic vaccination. We previously demonstrated that a non-replicating MVA encoding CD40 ligand (CD40L) enhances immune cell activation and function, triggers potent antitumor CD8 + T responses in different murine tumor models. Antitumor efficacy was increased when combined targeting antibodies. Here we report development TAEK-VAC-HerBy (TVH),...
The immunological outcome of infections and vaccinations is largely determined during the initial first days in which antigen-presenting cells instruct T to expand differentiate into effector memory cells. Besides essential stimulation T-cell receptor complex a plethora co-stimulatory signals not only ensures proper activation but also instils phenotypic functional characteristics appropriate fight off invading pathogen. tumour necrosis factor receptor/ligand pair CD27/CD70 gained lot...
The H3K9me3-specific histone methyltransferase SETDB1 is critical for proper regulation of developmental processes, but the underlying mechanisms are only partially understood. Here, we show that deletion Setdb1 in mouse fetal liver hematopoietic stem and progenitor cells (HSPCs) results compromised cell function, enhanced myeloerythroid differentiation, impaired lymphoid development. Notably, -deficient HSPCs exhibit reduced quiescence increased proliferation, accompanied by acquisition a...
Background: Our understanding of the interaction between host immune system and cancer has evolved rapidly over previous 10 years due to clinical success induced by checkpoint inhibition. Previous immunologic work can now be realized in combination strategies. Modified Vaccinia Ankara (MVA) offers significant opportunities its natural induction innate adaptive immunity, large payload, excellent safety profile. Methods: MVA vectors were administered subcutaneously (SC), intravenously (IV) or...
<h3>Background</h3> Virus-based vaccines and appropriate costimulation potently enhance antigen-specific T cell immunity against cancer. In the present study, we exploit both innate adaptive immune responses triggered by a novel recombinant modified vaccinia virus Ankara (rMVA) encoding Tumor-Associated Antigen (TAA) costimulatory CD40L solid tumors in combination regimes to overcome tumor-induced resistance immunotherapy. <h3>Material Methods</h3> Subcutaneous murine were induced C57BL/6 or...
Abstract Autoreactive CD4+ T cells are censored by two mechanisms, the so-called clonal deletion and deviation into regulatory in thymus both requiring same stimulus, namely interaction with self-peptide. In order to study mechanisms of central peripheral tolerance that operate shape CD4 T-cell repertoire, we have generated a TCR transgenic mouse specific for myelin proteolipid protein (PLP). We found PLP-specific undergo Treg differentiation concomitantly upon encounter cognate self-antigen...
Abstract In the last decade, immunotherapy has revolutionized cancer treatment. However, lack of potent therapy-induced immune responses against solid tumors due to immune-suppressive tumor microenvironment (TME) is still a major drawback. One approach reprogram TME virotherapy, which can target via destruction infected cells as well activating cell populations in TME. A versatile and safe tool for virotherapy modified vaccinia virus Ankara (MVA), already been approved by FDA non-replicating...
Abstract Peritoneal carcinomatosis is an advanced stage of cancer developed in the peritoneal cavity without effective treatment. In order to restore antitumor immunity subverted by tumor cells, we evaluated this study intraperitoneal administration vaccinia virus Ankara (MVA) genetically modified express proinflammatory cytokine single-chain interleukin 12. MVA encoding scIL-12 was models based on cells. The immune response ELISpot, flow cytometry, intravital microscopy, and depleting...