A5051821143- Diabetes and associated disorders
- Cancer Immunotherapy and Biomarkers
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Pancreatic function and diabetes
- Melanoma and MAPK Pathways
- CAR-T cell therapy research
- Phagocytosis and Immune Regulation
- Angiogenesis and VEGF in Cancer
- Diabetes Management and Research
- Cancer, Stress, Anesthesia, and Immune Response
- Heat shock proteins research
- Cancer Mechanisms and Therapy
- Immunotherapy and Immune Responses
- Cancer, Hypoxia, and Metabolism
- Nanoplatforms for cancer theranostics
- Protease and Inhibitor Mechanisms
- Cell Adhesion Molecules Research
- Diabetes Treatment and Management
- Cancer Cells and Metastasis
- Cutaneous Melanoma Detection and Management
- Escherichia coli research studies
- Cancer Research and Treatments
- IL-33, ST2, and ILC Pathways
- Immune cells in cancer
University of Bergen
2014-2024
Haukeland University Hospital
2012-2024
Joslin Diabetes Center
2017-2023
Harvard University
2015-2023
University Hospital Ulm
2010-2018
Johannes Gutenberg University Mainz
2018
University Medical Center of the Johannes Gutenberg University Mainz
2018
Universität Ulm
2016
Klinik für Psychosomatik
2004
VEGF driven angiogenesis plays a key role in cancer progression. We determined the clinical efficacy of bevacizumab monotherapy patients with metastatic melanoma.Thirty-five melanoma progression were enrolled this phase II, single arm trial. Each patient received 10 mg/kg q14 d until intolerable toxicity or disease occurred. Clinical was evaluated as objective response, control (DC), and survival. observed one complete (3%) 5 partial (14%) responses. In addition, experienced stable >6 months...
Bevacizumab is included in an increasing number of clinical trials. To find biomarkers to predict and monitor treatment response, cancer angiogenesis relevant mutations tumour circulating DNA (ctDNA) were investigated 26 metastatic melanoma patients treated with bevacizumab. Patients >1% BRAF/NRAS ctDNA at start had significantly decreased progression free survival (PFS) overall (OS) (PFS: p = 0.019, median 54 vs 774 days, OS: 0.026, 209 1064 days). during showed similar results 0.002,...
OBJECTIVE RIP-B7.1 mice expressing the costimulator molecule B7.1 (CD80) on pancreatic β-cells are a well established model to characterize preproinsulin-specific CD8 T-cell responses and experimental autoimmune diabetes (EAD). Different immunization strategies could prime T-cells in wild-type C57BL/6 (B6) mice, but did not induce diabetes. We tested whether altering B7-H1 (PD-L1) coinhibition can reveal diabetogenic potential of T-cells. RESEARCH DESIGN AND METHODS DNA-based adoptive...
Abstract Type 1 diabetes (T1D) results from the autoimmune destruction of pancreatic beta cells and is partly caused by deficiencies in Foxp3 + regulatory T‐cell (Treg) compartment. Conversely, therapies that increase Treg function can prevent animal models. The majority Tregs develop thymus (tTregs), but a proportion generated periphery (pTregs) − CD4 precursors. Whether pTregs play distinct role T1D has not yet been explored. We report here are key modifier disease nonobese diabetic (NOD)...
Ipilimumab was the first treatment that improved survival in advanced melanoma. Efficacy and toxicity a real-world setting may differ from clinical trials, due to more liberal eligibility criteria less intensive monitoring. Moreover, high costs lack of biomarkers have raised cost-benefit concerns about ipilimumab national healthcare systems limited its use. Here, we report prospective, interventional study, Ipi4 (NCT02068196), which aimed investigate efficacy population with This national,...
Abstract Background Vascular endothelial growth factor (VEGF) was initially known as vascular permeability and identified a driver of tumour angiogenesis. Recently, its role in supporting an immunosuppressive microenvironment demonstrated, anti‐VEGF treatment combined with immune checkpoint blockade is currently investigated. Further, beta‐adrenergic signalling modifier cancer hallmarks like response, angiogenesis metastasis gained increased attention during past years. Methods Focusing on...
Angiogenesis is important for the progression of cutaneous melanoma. Here, we analyzed prognostic impact angiogenic factor urokinase plasminogen activator resecptor (uPAR), vascular proliferation index (VPI) and tumor necrosis as a measure hypoxia in patient series nodular melanomas (n = 255) matched loco-regional metastases 78). Expression uPAR was determined by immunohistochemistry VPI assessed dual using Factor-VIII/Ki67 staining. Necrosis recorded based on HE-slides. As novel findings,...
The aim of this study was to identify potential predictive biomarkers in 35 patients with metastatic melanoma treated anti-angiogenic bevacizumab monotherapy a clinical phase II study. immunohistochemical expression various angiogenic factors tissues from primary melanomas and metastases as well their concentration blood samples were examined. Strong Heat Shock Protein 27 (HSP27) correlated significantly complete or partial response (p = 0.044). Furthermore, benefit, i.e., stable disease for...
Abstract DNA vaccination is a promising strategy to induce effector T cells but also regulatory Foxp3 + CD25 CD4 Treg and inhibit autoimmune disorders such as type 1 diabetes. Little known about the antigen requirements that facilitate priming of not autoreactive CD8 cells. We have shown injection preproinsulin (ppins)-expressing pCI/ppins vector into PD-1- or PD-L1-deficient mice induced K b /A12-21-monospecific A pCI/ppinsΔA12-21 (lacking critical /A12-21 epitope) did diabetes elicited...
Abstract Regulatory T cells (Tregs) protect against autoimmunity. In type 1 diabetes (T1D), Tregs slow the progression of beta cell autoimmunity within pancreatic islets. Increasing potency or frequency can prevent diabetes, as evidenced by studies in nonobese diabetic (NOD) mouse model for T1D. We report herein that a significant proportion islets NOD mice express Gata3 . The expression was correlated with presence IL-33, cytokine known to induce and expand + Tregs. Despite significantly...
Abstract The incidence of malignant melanoma is rising worldwide and survival for metastatic disease still poor. Recently, new treatment options have become available. Still, predictive biomarkers are needed to optimise this patient group. In study, we investigated the value 60 angiogenic factors in patients with treated anti‐vascular endothelial growth factor A antibody bevacizumab. Thirty‐five were included a clinical phase II trial baseline serum samples analysed by multiplex protein...
Coinhibitory PD-1/PD-L1 (B7-H1) interactions provide critical signals for the regulation of autoreactive T-cell responses. We established mouse models, expressing costimulator molecule B7.1 (CD80) on pancreatic beta cells (RIP-B7.1 tg mice) or are deficient in coinhibitory PD-L1 PD-1 molecules (PD-L1(-/-) and PD-1(-/-) mice), to study induction preproinsulin (ppins)-specific CD8 responses experimental autoimmune diabetes (EAD) by DNA-based immunization. RIP-B7.1 mice allowed us identify two...
CD5 is constitutively expressed on all T cells and a negative regulator of lymphocyte function. However, the full extent function in immunity remains unclear. deficiency impacts thymic selection extra-thymic regulatory cell generation, yet knockout was reported to cause no immune pathology. Here we show that key modulator gut immunity. We generated mice with inducible knockdown (KD) autoimmune-prone nonobese diabetic (NOD) background. caused cell-dependent wasting disease driven by chronic...
9548 Background: Upregulation of the receptor tyrosine kinase Axl has been linked with both a reduced response to PD-1 blockade and development therapy resistance BRAF directed therapies in melanoma. Bemcentinib (BGB324) is first-in-class orally bioavailable selective inhibitor which currently explored several ph II clinical trials. BGBIL006 (NCT02872259) an open label phase Ib/II trial designed explore whether combination bemcentinib improves ORRs standard care pts metastatic melanoma (MM)....
DNA vaccines against autoimmune type 1 diabetes (T1D) contain a nonpredictable risk to induce autoreactive T cell responses rather than protective immunity. Little is known if (and how) antigen expression and processing requirements favor the induction of or immune by immunization. Here, we analyzed whether structural properties preproinsulin (ppins) variants and/or subcellular targeting ppins designer antigens influence priming effector CD8+ Primarily, used H-2b RIP-B7.1 tg mice, expressing...
Abstract Type 1 diabetes (T1D) results from the autoimmune destruction of pancreatic beta cells and is partly caused by deficiencies in Foxp3 + regulatory T cell (Treg) compartment. Conversely, therapies that increase Treg function can prevent animal models. The majority Tregs develop thymus (tTregs), but a proportion generated periphery (pTregs) - CD4 precursors. Whether pTregs play distinct role T1D has not yet been explored. We report here are key modifier disease nonobesed diabetic (NOD)...
Abstract Purpose VEGF driven angiogenesis plays a key role in tumor growth. We determined clinical efficacy of bevacizumab monotherapy unselected patients with metastatic melanoma. Patients and methods Thirty-five melanoma progression were enrolled this phase II, single arm trial. Each patient received 10 mg/kg q14 d until intolerable toxicity or disease occurred. Clinical was evaluated by measuring objective response (OR), control (DC), survival. also potential predictive value parameters...