A5063891384- Glioma Diagnosis and Treatment
- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Cancer Genomics and Diagnostics
- Ocular Oncology and Treatments
- Melanoma and MAPK Pathways
- Mathematical Biology Tumor Growth
- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Brain Metastases and Treatment
- Cancer, Hypoxia, and Metabolism
- Angiogenesis and VEGF in Cancer
- Eosinophilic Esophagitis
- Glaucoma and retinal disorders
- Renal cell carcinoma treatment
- Bladder and Urothelial Cancer Treatments
- Immune cells in cancer
- IL-33, ST2, and ILC Pathways
- Cancer Cells and Metastasis
- Computational Drug Discovery Methods
- MicroRNA in disease regulation
- Protein Degradation and Inhibitors
- Cancer Research and Treatments
- Adenosine and Purinergic Signaling
- Neuroinflammation and Neurodegeneration Mechanisms
University Hospital Bonn
2020-2024
University of Bonn
2021-2024
Deutschen Konsortium für Translationale Krebsforschung
2017-2018
Essen University Hospital
2017-2018
Heinrich Heine University Düsseldorf
2017-2018
Düsseldorf University Hospital
2017-2018
Abstract The chemokine CXCL12 promotes glioblastoma (GBM) recurrence after radiotherapy (RT) by facilitating vasculogenesis. Here we report outcomes of the dose-escalation part GLORIA (NCT04121455), a phase I/II trial combining RT and CXCL12-neutralizing aptamer olaptesed pegol (NOX-A12; 200/400/600 mg per week) in patients with incompletely resected, newly-diagnosed GBM lacking MGMT methylation. primary endpoint was safety, secondary endpoints included maximum tolerable dose (MTD),...
Conjunctival melanoma is a potentially deadly eye tumour. Despite effective local therapies, tumour recurrence and metastasis remain frequent. The genetics of conjunctival melanomas incompletely understood.A large cohort 63 was screened for gene mutations known to be important in other subtypes by targeted next-generation sequencing. Mutation status correlated with patient prognosis.Frequent genes activating the MAP kinase pathway were identified. NF1 most frequent (n = 21, 33%). Recurrent...
Poor clinical responses to checkpoint blockade with anti-CTLA-4 and anti-PD-1 antibodies in melanoma have recently been associated acquired IFNγ resistance that protects tumor cells from the antiproliferative pro-apoptotic cytokine activity. IFNγ-resistant very often lack functional expression of signaling pathway gene JAK2 due deletions or inactivating mutations. Analyzing cell lines (n = 46, applying next-generation targeted sequencing single nucleotide polymorphism arrays) as well...
Group 1 innate lymphoid cells (ILCs) comprise a heterogeneous family of cytotoxic natural killer (NK) and ILC1s. We identify population "liver-type" ILC1s with transcriptional, phenotypic, functional features distinct from those conventional liver-resident NK as well other previously described human ILC1 subsets. LT-ILC1s are CD49a+CD94+CD200R1+, express the transcription factor T-BET, do not activating receptor NKp80 or EOMES. Similar to cells, liver-type produce IFN-γ, TNF-α, GM-CSF;...
Background Immune responses against tumors are subject to negative feedback regulation. checkpoint inhibitors (ICIs) blocking Programmed cell death protein 1 (PD-1), a receptor expressed on T cells, or its ligand PD-L1 have significantly improved the treatment of cancer, in particular malignant melanoma. Nevertheless, and durability variables, suggesting that additional critical mechanisms exist need be targeted improve therapeutic efficacy. Methods We used different syngeneic melanoma mouse...
Clear cell renal carcinoma (ccRCC) is the most common cancer accounting for 80% of all cancers as well majority cancer-associated deaths. During last decade, treatment paradigm ccRCC has radically changed. In particular, recent development immune checkpoint inhibitors led to an increased overall survival in metastatic setting. Moreover, novel therapies targeting tumor microenvironment have been developed. this rapidly evolving landscape, precise tools personalized therapy are needed. Here,...
The most common malignant intraocular tumors with a high mortality in adults are uveal melanomas. Uveal melanomas arise frequently the choroid or ciliary body (97%) and rarely iris (3%). Whereas conjunctival posterior (ciliary choroidal) have been studied more detail genetically, little data exist regarding melanomas.In our study, we genetically analyzed 19 melanomas, 8 3 ring 4 nevi. A targeted next-generation sequencing approach was applied, covering mutational hotspot regions of nine...
The profound but frequently transient clinical responses to BRAFV600 inhibitor (BRAFi) treatment in melanoma emphasize the need for combinatorial therapies. Multiple trials combining BRAFi and immunotherapy are under way further enhance therapeutic responses. However, which extent inhibition may affect immunogenicity over time remains largely unknown. To support development of an optimal protocol, we studied impact prolonged exposure on recognition cells by T different patient models. We...
CD73 is the key enzyme in generation of extracellular adenosine, a mediator involved tumor progression, immune escape and resistance to anti-cancer therapeutics. Microenvironmental conditions influence expression cells. However how activity regulated stress condition lower nutrient availability are largely unknown. Our results indicate that serum starvation leads marked up-regulation on A375 melanoma cells time-dependent manner. The cell-surface associated with an increased release TGF-β1 by...
2048 Background: Standard of care (SOC) treatment achieves poor clinical outcomes in patients with glioblastoma (GBM), particularly the absence MGMT promoter hypermethylation. Preclinical models suggest that GBM recurrence is facilitated by CXCL12-mediated recruitment bone marrow-derived cells capable vasculogenesis after radiotherapy (RT). We have recently reported favorable safety and feasibility data phase I/II GLORIA trial, which combines RT CXCL12-neutralizing L-RNA aptamer olaptesed...
2050 Background: Pre-clinical studies consistently demonstrate that inhibition of the CXCL12/CXCR4/CXCR7 axis abrogates recruitment pro-vasculogenic bone marrow-derived cells after radiotherapy (RT) glioblastoma (GBM) and promotes T cell exclusion from tumor microenvironment (TME). The German multicenter phase 1/2 trial GLORIA (NCT04121455) assesses safety RT plus escalating dose levels (DL) CXCL12-neutralizing RNA-Spiegelmer Olaptesed pegol (OLA; NOX-A12) in patients with...
The interaction of glioblastoma (GB) and microglia is critical due to its implications for tumor progression, immune response modulation, potential therapeutic strategies. However, the role in GB pathogenesis remains unclear, especially regarding vivo dynamics their interplay. Performing three-photon imaging an autochthonous, immunocompetent mouse model, we examined tumor/microglia within previously inaccessible regions at far infiltration zone corpus callosum. Initially, increased tissue...
Abstract BACKGROUND We recently reported favorable safety and preliminary efficacy signals for treatment with radiotherapy (RT), the CXCL12 neutralizing L-RNA aptamer olaptesed pegol (NOX-A12) bevacizumab glioblastoma (GBM) in German multicenter phase 1/2 GLORIA trial (NCT04121455). Here, we report updated outcomes on dual inhibition of vasculogenesis angiogenesis (bevacizumab). METHODS Six patients incompletely resected, MGMT-unmethylated GBM, ECOG≤ 2 were enrolled, receiving standard RT...
Introduction In recent years, treatment with immunomodulating antibodies targeting the inhibitory T-cell receptor PD-1 led to durable clinical responses in a subgroup of patients melanoma, lung cancer or bladder cancer. Nevertheless, majority do not respond, and mechanisms underlying primary acquired resistance are still poorly defined. Recently, it was demonstrated that mutations JAK1/2-STAT1 signalling pathway play an essential role protecting tumour cells from anti-proliferative...
Abstract BACKGROUND We recently reported favorable safety, promising clinical efficacy and immunohistochemical indicators of response after radiotherapy (RT) plus escalating doses the CXCL12-neutralizing RNA-Spiegelmer olaptesed pegol (NOX-A12) for glioblastoma in German multicenter phase 1/2 GLORIA trial (NCT04121455). Here, we report outcomes RT dual inhibition vasculogenesis angiogenesis (bevacizumab). METHODS After establishing safety monotherapy arm, enrolled six patients with...
Abstract BACKGROUND Preclinical studies showed that CXCL12-mediated influx of highly angiogenic monocytes/macrophages is a key driver tumor re-vascularization and re-growth after radiotherapy (RT) glioblastoma (GBM). We report findings from phase I/II proof-of concept (PoC) study on CXCL12 inhibition during RT GBM. METHODS Patients ≥18years with incompletely or unresected GBM without MGMT promoter hypermethylation ECOG≤2 were eligible to participate. received continuous (24/7) i.v. infusions...