A5019930673- Glioma Diagnosis and Treatment
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Heat shock proteins research
- Immune Cell Function and Interaction
- Brain Metastases and Treatment
- Cancer, Hypoxia, and Metabolism
- Cancer Immunotherapy and Biomarkers
- Cancer Research and Treatments
- Prostate Cancer Treatment and Research
- Histone Deacetylase Inhibitors Research
- Cancer Genomics and Diagnostics
- RNA Interference and Gene Delivery
- Vascular Malformations Diagnosis and Treatment
- Virus-based gene therapy research
- Endoplasmic Reticulum Stress and Disease
- Colorectal Cancer Treatments and Studies
- Epigenetics and DNA Methylation
- Vitamin D Research Studies
- Radiomics and Machine Learning in Medical Imaging
- Cancer Cells and Metastasis
- Monoclonal and Polyclonal Antibodies Research
- Protein Degradation and Inhibitors
- Management of metastatic bone disease
- Transgenic Plants and Applications
University Hospital Frankfurt
2016-2025
Goethe University Frankfurt
2016-2025
Frankfurt Cancer Institute
2015-2025
German Cancer Research Center
2015-2025
Heidelberg University
2015-2025
Deutschen Konsortium für Translationale Krebsforschung
2015-2024
Senckenberg Research Institute and Natural History Museum Frankfurt/M
2016-2024
Goethe Institute
2016-2023
Broad Institute
2016-2021
University Hospital Heidelberg
2017
Glioblastoma (GBM) is the most common and malignant intracranial tumor in adults currently incurable. To specifically target natural killer (NK) cell activity to GBM, we employed NK-92/5.28.z cells that are continuously expanding human NK expressing an ErbB2-specific chimeric antigen receptor (CAR). ErbB2 expression 56 primary tumors, four cultures, seven established lines was assessed by immunohistochemistry flow cytometry. Cell killing of analyzed vitro cytotoxicity assays. In vivo...
Abstract Background Glioblastoma (GB) is incurable at present without established treatment options for recurrent disease. In this phase I first-in-human clinical trial we investigated safety and feasibility of adoptive transfer clonal chimeric antigen receptor (CAR)-NK cells (NK-92/5.28.z) targeting HER2, which expressed elevated levels by a subset glioblastomas. Methods Nine patients with HER2-positive GB were treated single doses 1 × 107, 3 or 108 irradiated CAR-NK injected into the...
Epidermal growth factor receptor (EGFR) and its mutant form EGFRvIII are overexpressed in a large proportion of glioblastomas (GBM). Immunotherapy with an EGFRvIII-specific vaccine has shown efficacy against GBM clinical studies. However, immune escape by antigen-loss variants lack control EGFR wild-type positive clones limit the usefulness this approach. Chimeric antigen (CAR)-engineered natural killer (NK) cells may represent alternative immunotherapeutic strategy. For targeting to GBM, we...
Malignant gliomas exhibit a high intrinsic resistance against stimuli triggering apoptotic cell death. HSF1 acts as transcription factor upstream of HSP70 and the co-chaperone BAG3 that is overexpressed in glioblastoma. To specifically target this mechanism, we applied selective inhibitor KRIBB11 HSP70/BAG3 interaction YM-1 combination with pan-Bcl-2 AT-101. Here, demonstrate lentiviral silencing significantly enhances AT-101-induced death reactivates effector caspase-mediated apoptosis U251...
BRAF V600E mutations occur frequently in malignant melanoma, but are rare most glioma subtypes. Besides, more benign brain tumors such as ganglioglioma, dysembryoblastic neuroepithelial tumours and supratentorial pilocytic astrocytomas, only pleomorphic xanthoastrocytomas (50-78%) epitheloid glioblastoma (50%) regularly exhibit mutations. In the present study, we report on three patients with recurrent gliomas harbouring a mutation. All presented markedly disseminated leptomeningeal disease...
Abstract Purpose: BAY1436032, an inhibitor of mutant isocitrate dehydrogenase 1 (mIDH1), was active against multiple IDH1-R132X solid tumors in preclinical models. This first-in-human study designed to determine the safety and pharmacokinetics evaluate its potential pharmacodynamics antitumor effects. Patients Methods: The comprised dose escalation expansion cohorts. BAY1436032 tablets were orally administered twice daily on a continuous basis subjects with mIDH1 tumors. Results: In...
In previous trials, bevacizumab failed to prolong the overall survival time in newly diagnosed glioblastoma and at first recurrence. Randomized clinical trials second or further recurrence following failure of radiotherapy, temozolomide lomustine, retrospective analyses focusing on this specific cohort, are not yet available. A total 62 patients with who received after standard care, including were retrospectively identified. Patient characteristics, treatment details, concomitant therapy,...
Glioblastoma (GB) is the most common primary brain tumor, which characterized by low immunogenicity of tumor cells and prevalent immunosuppression in microenvironment (TME). Targeted local combination immunotherapy a promising strategy to overcome these obstacles. Here, we evaluated tumor-cell specific delivery an anti-PD-1 immunoadhesin (aPD-1) via targeted adeno-associated viral vector (AAV) as well HER2-specific NK-92/5.28.z (anti-HER2.CAR/NK-92) components for immunotherapy. In...
Molecular mimicry between commensal bacterial antigens and tumor-associated (TAAs) has shown potential in enhancing antitumor immune responses. This study leveraged this concept using antigens, termed OncoMimics, to induce TAA-derived peptide (TAAp)-specific cross-reactive cytotoxic T cells improve the efficacy of peptide-based immunotherapies. The discovery OncoMimics primarily relied on a bioinformatics approach identify bacteria-derived sequences mimicking TAAps. Several (OMP) candidates...
Abstract Background Glioblastoma is the most aggressive primary brain tumor with limited efficacy of established therapies, and a pronounced immunosuppressive microenvironment. Targeting HER2 local immunotherapy allows for high specificity in physiologically very low expression. Monotherapy CAR-NK cells targeted against has previously shown medium-sized GL261/HER2 tumors. Methods Advanced tumors were treated by cell injection combined systemic anti-PD-1 checkpoint blockade. Tumor growth...
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Glioblastoma is the most frequent and malignant primary brain tumor. Even in subgroup with O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation favorable response to first-line therapy, survival after relapse short (12 months). Standard therapy for recurrent MGMT-methylated glioblastoma not standardized may consist of re-resection, re-irradiation, chemotherapy temozolomide (TMZ), lomustine (CCNU), or a combination thereof. Preclinical results show that meclofenamate (MFA),...
Although inhibition of the epidermal growth factor receptor is a plausible therapy for malignant gliomas that, in vitro, enhances apoptosis, results clinical trials have been disappointing. The mammalian target rapamycin (mTOR) serine/threonine kinase that integrates starvation signals and generates adaptive responses aim at maintenance energy homeostasis. Antagonism mTOR has suggested as strategy to augment efficacy by interfering with deregulated signalling cascades downstream Akt. Here we...
Recently, the conserved intracellular digestion mechanism 'autophagy' has been considered to be involved in early tumorigenesis and its blockade proposed as an alternative treatment approach. However, there is ongoing debate about whether blocking autophagy positive or negative effects tumor cells. Since only poor data clinico-pathological relevance of gliomas vivo, we first established a cell culture based platform for vivo detection autophago-lysosomal components. We then investigated key...
The peroxisome proliferator-activated receptor γ coactivator (PGC)-1α is a master regulator of mitochondrial biogenesis and controls metabolism by coordinating transcriptional events. Here, we interrogated whether PGC-1α involved in tumor growth the metabolic flexibility glioblastoma cells. was expressed subset established glioma cell lines primary cultures. Furthermore, higher expression associated with an adverse outcome TCGA dataset. Suppression shRNA PGC-1α-positive U343MG line...
Glioblastoma (GBM) is the most common and aggressive primary brain tumor, with a very high rate of recurrence median survival 15 months after diagnosis. Abundant evidence suggests that certain sub-population cancer cells harbors stem-like phenotype likely responsible for disease recurrence, treatment resistance potentially even infiltrative growth GBM. GBM incidence has been negatively correlated serum levels 25-hydroxy-vitamin D3, while low pH within tumors shown to promote expression...
Molecular diagnostics including next generation gene sequencing are increasingly used to determine options for individualized therapies in brain tumor patients. We aimed evaluate the decision-making process of molecular targeted and analyze data on tolerability as well signals efficacy.Via retrospective analysis, we identified primary patients who were treated off-label with a therapy at University Hospital Frankfurt, Goethe University. analyzed which types alterations utilized guide...
Current pathological diagnostics include the analysis of (epi-)genetic alterations as well oncogenic pathways. Deregulated mammalian target rapamycin complex 1 (mTORC1) signaling has been implicated in a variety cancers including malignant gliomas and is considered promising cancer treatment. Monitoring mTORC1 activity before during inhibitor therapy essential. The aim our study to provide recommendation report on pitfalls use phospho-specific antibodies against mTORC1-targets phospho-RPS6...
Leptomeningeal dissemination of a primary brain tumor is condition which challenging to treat, as it often occurs in rather late disease stages highly pretreated patients. Its prognosis dismal and there still no accepted standard care. We report here good clinical effect with partial response three out nine patients stable improvement on symptoms two more following systemic anti-angiogenic treatment bevacizumab (BEV) alone or combination chemo- and/or radiotherapy series leptomeningeal from...
Adenosine monophosphate (AMP)‑activated protein kinase (AMPK) is a major cellular energy sensor that activated by an increase in the AMP/adenosine triphosphate (ATP) ratio. This causes initiation of adaptive programs, leading to inhibition anabolic pathways and increasing ATP synthesis. AMPK indirectly inhibits mammalian target rapamycin (mTOR) complex 1 (mTORC1), serine/threonine central regulator cell growth metabolism, which integrates various inhibitory signals, such as depletion...
In patients with glioblastoma, antiangiogenic therapy bevacizumab (BEV) has been shown to improve progression-free survival (PFS), but not overall (OS). Especially in an unusual infiltrative phenotype as seen multifocal the use of BEV is still more controversial. Therefore, we prepared a retrospective case series 16 suffering from glioblastoma treated BEV. We compared these matched control cohort single lesion The objective this study was evaluate whether course disease differs pattern those...