A5016964659- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Glioma Diagnosis and Treatment
- Heat shock proteins research
- Cancer Immunotherapy and Biomarkers
- Immune Cell Function and Interaction
- Cancer Research and Treatments
- Brain Metastases and Treatment
- Endoplasmic Reticulum Stress and Disease
- T-cell and B-cell Immunology
- RNA Interference and Gene Delivery
- Multiple Sclerosis Research Studies
- Single-cell and spatial transcriptomics
- MicroRNA in disease regulation
- Cancer Genomics and Diagnostics
- PARP inhibition in cancer therapy
- Virus-based gene therapy research
- Radiation Therapy and Dosimetry
- Hormonal Regulation and Hypertension
- interferon and immune responses
- Transgenic Plants and Applications
- Autophagy in Disease and Therapy
- Angiogenesis and VEGF in Cancer
- Advanced X-ray and CT Imaging
- MRI in cancer diagnosis
Goethe University Frankfurt
2015-2025
University Hospital Frankfurt
2020-2025
German Cancer Research Center
2014-2024
Heidelberg University
2014-2024
University Hospital Heidelberg
2017-2024
Bernstein Center for Computational Neuroscience Heidelberg-Mannheim
2022-2024
University Medical Centre Mannheim
2018-2024
Medizinische Fakultät Mannheim
2022-2024
Heidelberg University
2024
University of Mannheim
2024
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...
Substitution of lysine 27 to methionine in histone H3 (H3K27M) defines an aggressive subtype diffuse glioma. Previous studies have shown that a H3K27M-specific long peptide vaccine (H3K27M-vac) induces mutation-specific immune responses control H3K27M+ tumors major histocompatibility complex-humanized mice. Here we describe first-in-human treatment with H3K27M-vac eight adult patients progressive midline glioma on compassionate use basis. Five received combined anti-PD-1 based physician's...
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...
Primary central nervous system (CNS) gliomas can be classified by characteristic genetic alterations. In addition to solid tissue obtained via surgery or biopsy, cell-free DNA (cfDNA) from cerebrospinal fluid (CSF) is an alternative source of material for genomic analyses.
H3K27M, a driver mutation with T and B cell neoepitope characteristics, defines an aggressive subtype of diffuse glioma poor survival. We functionally dissect the immune response one patient treated H3K27M peptide vaccine who subsequently entered complete remission. The robustly expanded class II human leukocyte antigen (HLA)–restricted peripheral H3K27M-specific cells. Using functional assays, we characterized 34 clonally unique H3K27M-reactive receptors identified critical, conserved...
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...
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...
Model-Based Iterative Reconstruction in CT EnterographyKevin P. Murphy1,2, Lee Crush1, Maria Twomey1,2, Patrick D. McLaughlin3, Iris C. Mildenberger2, Niamh Moore1, Jackie Bye4, Owen J. O'Connor1,2, Sean E. McSweeney1, Fergus Shanahan5 and Michael M. Maher1,2Audio Available | Share
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...
Background: There is little information concerning the invasive coronary angiography (ICA) findings of patients with acute ischemic stroke (AIS) or transient attack (TIA) elevated troponin levels and suspected myocardial infarction (MI). This study analyzed patient characteristics associated ICA outcomes. Methods: A total 8,322 AIS TIA, treated between March 2010 May 2020, were retrospectively screened for serum I at hospital admission. Patients in whom was performed, due to type 1 MI based...
TPS2095 Background: Glioblastoma (GBM) is characterized by a low mutational burden limiting the number of neoantigen targets for cancer vaccines. Vaccination against tumor-associated antigens over-presented via MHC class I and II in GBM an alternative that has shown promise previous trials. A vaccine containing peptides presented HLA-A*02:01 (class I) some DR alleles II), showed evidence peripheral intratumoral vaccine-induced immune response these patients with GBM. Our study will assess...
Diffuse midline gliomas (DMG) are universally lethal central nervous system tumors that carry almost unanimously the clonal driver mutation histone-3 K27M (H3K27M). The single amino acid substitution of lysine to methionine harbors a neoantigen is presented in tumor tissue. long peptide vaccine H3K27M-vac targeting this major histocompatibility complex class II (MHC II)-restricted induces mutation-specific immune responses suppress growth H3K27M+ flank an MHC-humanized rodent model.INTERCEPT...
Bevacizumab has been shown to improve progression-free survival and neurologic function, but failed overall in newly diagnosed glioblastoma at first recurrence. Nonetheless, bevacizumab is widely used patients with recurrent glioma. However, its use gliomas showing a gliomatosis cerebri growth pattern contentious. Due the marked diffuse infiltrative less angiogenic tumor growth, it may appear questionable whether can have therapeutic effect those patients. development of nodular, necrotic,...
2034 Background: EO2401 (EO) was designed to activate existing commensal memory T-cells cross-reacting with tumor associated antigens (TAAs). EO includes microbial-derived, synthetically produced peptides corresponding HLA-A2 restricted epitopes molecular mimicry three TAAs upregulated in glioblastoma (GB), IL13Rα2, BIRC5 and FOXM1, the CD4 helper peptide UCP2 adjuvant Montanide. Pre-clinically generates strong immune responses cross-reactive CD8 cells recognizing TAAs. Methods: This ongoing...
Abstract H3K27M, a driver mutation with T- and B-cell neoepitope characteristics, defines an aggressive subtype of diffuse glioma poor survival. We functionally dissect the immune response one patient who was treated H3K27M peptide vaccine subsequently entered complete remission. The robustly expanded class II HLA-restricted peripheral H3K27M-specific T cells. Using functional assays, we characterized 34 clonally unique H3K27M-reactive cell receptors identified critical, conserved motifs in...
Abstract EO2401 expands existing memory T cells recognizing protein sequences from gut bacteria, which cross-react with tumor associated antigens (TAAs). contains three CD8 HLA-A2 epitopes mimicry to glioblastoma-TAAs (IL13Rα2, BIRC5, and FOXM1) the CD4 epitope UCP2. Patients received (300μg/peptide, q2weeks x4, then every 4weeks) nivolumab (3mg/kg, q2weeks) in cohorts: C1a (n = 21, Ex2→EN; option for symptom directed low-dose bevacizumab [sLDB; 5mg/kg, q2weeks] as anti-edema treatment);...
Concurrent malignant brain tumors in patients with multiple sclerosis (MS) constitute a rare but paradigmatic phenomenon for studying neuroimmunological mechanisms from both molecular and clinical perspectives.A multicenter cohort of 26 diagnosed primary was studied disease localization, tumor treatment-related MS activity, characteristics specific diffuse glioma patients.MS neither predisposes nor protects the development gliomas. Patients glioblastoma WHO grade 4 without...
Abstract Peptide vaccines have emerged as a promising strategy for cancer immunotherapy, yet often lack of strong, specific and sustained immune responses against tumor antigens. To achieve robust response, the effective selection tumour antigens is crucial. While neoantigens trigger potent responses, their use suffers from patient specificity rarity in low-mutational tumors. Alternatively, immunogenic potential tumor-associated (TAAs) limited by central tolerance. Molecular mimicry T cell...