- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Acute Myeloid Leukemia Research
- Chronic Lymphocytic Leukemia Research
- CAR-T cell therapy research
- Antibiotic Resistance in Bacteria
- T-cell and B-cell Immunology
- vaccines and immunoinformatics approaches
- Chronic Myeloid Leukemia Treatments
- Cancer Immunotherapy and Biomarkers
- Bacterial Identification and Susceptibility Testing
- Immune Response and Inflammation
- RNA Interference and Gene Delivery
- Lymphoma Diagnosis and Treatment
- Clostridium difficile and Clostridium perfringens research
- Hematopoietic Stem Cell Transplantation
- Monoclonal and Polyclonal Antibodies Research
- Immune cells in cancer
- Antimicrobial Resistance in Staphylococcus
- Infections and bacterial resistance
- Cancer-related gene regulation
- Ubiquitin and proteasome pathways
- Immunodeficiency and Autoimmune Disorders
- Bladder and Urothelial Cancer Treatments
- Gut microbiota and health
Klinikum Region Hannover
2020-2024
University Children's Hospital Tübingen
2016-2024
University of Tübingen
2004-2023
German Cancer Research Center
2015-2020
Deutschen Konsortium für Translationale Krebsforschung
2020
Universitätsklinikum Tübingen
2017-2018
Heidelberg University
2015-2018
Ludwig-Maximilians-Universität München
2011
LMU Klinikum
2010
Abstract A phase I trial was conducted to evaluate the feasibility, safety, and efficacy of a dendritic cell–based vaccination in patients with metastatic renal cell carcinoma (RCC). Autologous mature cells derived from peripheral blood monocytes were pulsed HLA-A2-binding MUC1 peptides (M1.1 M1.2). For activation CD4+ T-helper lymphocytes, further incubated PAN-DR-binding peptide PADRE. Dendritic vaccinations done s.c. every 2 weeks for four times repeated monthly until tumor progression....
The selection pressure exercised by antibiotic drugs is an important consideration for the wise stewardship of antimicrobial treatment programs. Treatment decisions are currently based on crude assumptions, and there urgent need to develop a more quantitative knowledge base that can enable predictions impact individual antibiotics human gut microbiome resistome.Using shotgun metagenomics, we quantified changes in two cohorts hematological patients receiving prophylactic antibiotics; one...
Infections with multidrug-resistant bacteria often leave limited or no treatment options. The transfer of antimicrobial resistance genes (ARG) carrying plasmids between bacterial species by horizontal gene represents an important mode expansion ARGs. Here, we demonstrate the application Nanopore sequencing in a hospital setting for monitoring and rapid evolution antibiotic within across multiple species. In 2009, experienced outbreak extensively Pseudomonas aeruginosa harboring...
The fms-related tyrosine kinase 3 (FLT3) receptor has been extensively studied over the past two decades with regard to oncogenic alterations that do not only serve as prognostic markers but also therapeutic targets in acute myeloid leukemia (AML). Internal tandem duplications (ITDs) became of special interest this setting they are associated unfavorable prognosis. Because sequence-dependent protein conformational changes FLT3-ITD tends autophosphorylate and displays a constitutive...
Dendritic cells (DC) are the most potent antigen-presenting (APC) with unique ability to activate naïve T and initiate maintain primary immune responses. Immunosuppressive anti-inflammatory stimuli on DC such as cytokine IL-10 suppress activity of transcription factor NF-κB what results in downregulation costimulatory molecules, MHC production. Glycoprotein NMB (GPNMB) is a transmembrane protein, which acts coinhibitory molecule strongly inhibiting cell responses if present APC....
Pseudomonas putida is a Gram-negative, non-fermenting bacterium frequently encountered in various environmental niches. P. rarely causes disease humans, though serious infections and outbreaks have been reported from time to time. Some suggested that functions as an exchange platform for antibiotic resistance genes (ARG), thus represents concern the spread of ARGs more pathogenic organisms within hospital. Though poorly understood, frequency ARG between virulent aeruginosa its clinical...
Isavuconazole is a novel antifungal drug approved for the treatment of adults with invasive aspergillosis and mucormycosis. While azoles as class effect are known to prolong QTc interval, clinical trials have shown that isavuconazole administration may cause shortening in dose-related manner. Here, we assessed effects on length interval. The objective study was describe changes interval induced by treatment. A total 26 adult patients from 7 hospitals were included. Patients received fungal...
The TNF receptor family member OX40 promotes activation and proliferation of T cells, which fuels efforts to modulate this immune checkpoint reinforce antitumor immunity. Besides NK cells are a second cytotoxic lymphocyte subset that contributes immunity, particularly in leukemia. Accordingly, these being clinically evaluated for cancer treatment through multiple approaches, such as adoptive transfer ex vivo expanded polyclonal (pNKC). Here, we analyzed whether how its ligand (OX40L)...
Vancomycin-resistant Enterococcus faecium (VREfm) is a frequent cause of nosocomial outbreaks. In the second half 2015, sharp increase in incidence VREfm was observed at our university medical center. Next-generation sequencing (NGS) used to analyze first isolates recovered from patients between 2010 and 2016 (n = 773) order decipher epidemiological change, outbreak dynamics, possible transmission routes. were analyzed using whole-genome followed by sequence type extraction phylogenetic...
About half of AML patients achieving complete remission (CR) display measurable residual disease (MRD) and eventually relapse. FLYSYN is an Fc-optimized antibody for eradication MRD directed to FLT3/CD135, which abundantly expressed on cells.This first-in-human, open-label, single-arm, multicenter trial included in CR with persisting or increasing evaluated safety/tolerability, pharmacokinetics preliminary efficacy at different dose levels administered intravenously (cohort 1-5: single 0.5...
Abstract Background Active dendritic cell (DC) immunization protocols are rapidly gaining interest as therapeutic options in patients with acute myeloid leukemia (AML). Here we present for the first time a GMP-compliant 3-day protocol generation of monocyte-derived DCs using different synthetic Toll-like receptor (TLR) agonists intensively pretreated AML. Methods Four maturation cocktails were compared their impact on recovery, phenotype, cytokine secretion, migration, and lymphocyte...
Nine independent Gram-negative bacterial strains were isolated from rectal swabs or stool samples of immunocompromised patients two different wards a university hospital. All isolates phylogenetically analysed based on their 16S rRNA gene sequence, housekeeping recN, multilocus sequence analysis concatenated partial fusA, leuS, pyrG and rpoB sequences, by whole genome sequencing data. The the new species cluster together form separate branch with Citrobacter werkmanii NBRC105721T as most...
Background Evidence supporting the effectiveness of single-room contact precautions (SCP) in preventing in-hospital acquisition vancomycin-resistant enterococci (haVRE) is limited. Aim We assessed impact SCP on haVRE and their transmission. Methods conducted a prospective, multicentre cohort study German haematological/oncological departments during 2016. Two sites performed for VRE patients two did not (NCP). defined 5% haVRE-risk difference as non-inferiority margin, screened VRE,...
The introduction of idelalisib, ibrutinib and venetoclax for treatment chronic lymphocytic leukemia (CLL) has greatly improved long term survival patients. However, many patients do not achieve complete remission suffer from development resistance upon with these small molecule inhibitors. Here we report that the TNF family member B-cell activating factor (BAFF) mediates CLL cells to by sustaining preventing apoptosis malignant B as revealed analysis cellular ATP levels mitochondrial...
Transfection of dendritic cells (DCs) with RNA was shown to be effective in the generation antigen-specific T cells, probably due induction a polyclonal cell response directed against multiple antigens. To verify this assumption we used DCs, generated from cytomegalovirus (CMV)-negative or -positive donors, that were electroporated vitro-transcribed (in vitro transcript, IVT) coding for CMV pp65 antigen. We found transfection DCs IVT induces an expansion CD8+ lymphocytes recognize peptide...
OX40 and its ligand are members of the TNF/TNF receptor superfamily, which includes various molecules influencing cellular signaling function both tumor immune cells. The ability to promote proliferation differentiation activated T cells fueled present attempts modulate this checkpoint reinforce antitumor immunity. While we recently found evidence for involvement in pathophysiology acute myeloid leukemia including natural killer (NK) cell immunosurveillance, less is known on role...
Abstract Objectives We assessed the efficacy and safety of an oral antimicrobial regimen for short- long-term intestinal eradication ESBL-producing Escherichia coli Klebsiella pneumoniae (ESBL-EC/KP) in immunocompromised patients. Methods performed a randomized (2:1), double-blind multicentre Phase II study four haematology–oncology departments. Patients colonized with ESBL-EC/KP received 7 day colistin (2 × 106 IU 4×/day), gentamicin (80 mg 4×/day) fosfomycin (three administrations 3 g...