A5038659706- CAR-T cell therapy research
- Nanowire Synthesis and Applications
- Single-cell and spatial transcriptomics
- Spectroscopy Techniques in Biomedical and Chemical Research
- Glycosylation and Glycoproteins Research
- Ubiquitin and proteasome pathways
- Spectroscopy and Chemometric Analyses
- Cancer Immunotherapy and Biomarkers
- Virus-based gene therapy research
- Peptidase Inhibition and Analysis
- CRISPR and Genetic Engineering
- Neuroblastoma Research and Treatments
- Biosimilars and Bioanalytical Methods
- Immune Cell Function and Interaction
- Molecular Biology Techniques and Applications
- Sarcoma Diagnosis and Treatment
- Computational Drug Discovery Methods
- Viral Infectious Diseases and Gene Expression in Insects
- Macrophage Migration Inhibitory Factor
- Cardiac Valve Diseases and Treatments
- PARP inhibition in cancer therapy
- Extracellular vesicles in disease
- Reproductive System and Pregnancy
- RNA and protein synthesis mechanisms
- Inflammatory Biomarkers in Disease Prognosis
University Children's Hospital Tübingen
2021-2024
University of Tübingen
2021-2024
German Cancer Research Center
2024
University of British Columbia
2022
Uniwersytecki Szpital Dziecięcy
2020
Children's Clinical University Hospital
2020
Biotechnology Institute Thurgau
2018
University of Konstanz
2018
Immune-checkpoint inhibitors (ICI) have transformed oncological therapy. Up to 20% of all non-small cell lung cancers (NSCLCs) show durable responses upon treatment with ICI, however, robust markers predict therapy response are missing. Here we that blood platelets interact cancer cells and PD-L1 protein is transferred from tumor in a fibronectin 1, integrin α5β1 GPIbα-dependent manner. Platelets NSCLC patients found express platelet possess the ability inhibit CD4 CD8 T-cells. An algorithm...
Spatial transcriptomics of histological sections have revolutionized research in life sciences and enabled unprecedented insights into genetic processes involved tissue reorganization. However, contrast to genomic analysis, the actual biomolecular composition sample has fallen behind, leaving a gap potentially highly valuable information. Raman microspectroscopy provides untargeted spatiomolecular information at high resolution, capable filling this gap. In study we demonstrate spatially...
Abstract Targeting AML by chimeric antigen receptor T-cells (CAR-T) is challenging due to the promiscuous expression of AML-associated antigens in healthy hematopoiesis and high degree inter- intratumoral heterogeneity. Here, we present single-cell data 30 primary pediatric samples. We identified CD33, CD38, CD371, IL1RAP CD123 as most frequently expressed. Notably, variability was observed not only across different patient samples but also among leukemic cells same suggesting necessity...
Deciphering cellular components and the spatial interaction network of tumor immune microenvironment (TIME) solid tumors is pivotal for understanding biologically relevant cross-talks and, ultimately, advancing therapies. Multiplexed tissue imaging provides a powerful tool to elucidate complexity in holistic manner. We established cross-validated comprehensive immunophenotyping panel comprising over 121 markers multiplexed using MACSima™ cyclic staining (MICS) alongside an end-to-end...
Abstract FAT10 is a ubiquitin-like modifier that directly targets proteins for proteasomal degradation. Here, we report the high-resolution structures of two individual domains (UBD) are joined by flexible linker. While UBDs show typical ubiquitin-fold, their surfaces entirely different from each other and ubiquitin explaining unique binding specificities. Deletion linker abrogates FAT10-conjugation while its mutation blocks auto-FAT10ylation FAT10-conjugating enzyme USE1 but not bulk...
Chimeric antigen receptor (CAR)-T therapy holds great promise to sustainably improve cancer treatment. However, currently, a broad applicability of CAR-T cell therapies is hampered by limited versatility and tractability the lack exclusive target antigens discriminate cancerous from healthy tissues. To achieve temporal qualitative control on function, we engineered Adapter CAR (AdCAR) system. AdCAR-T are redirected surface via biotin-labeled adapter molecules in context specific linker...
Abstract This study presents a high-dimensional immunohistochemistry approach to assess human γδ T cell subsets in their native tissue microenvironments at spatial resolution, hitherto unmet scientific goal due the lack of established antibodies and required technology. We report an integrated based on multiplexed imaging bioinformatic analysis identify cells, characterize phenotypes, analyze composition microenvironment. Twenty-eight were identified samples from fresh frozen colon...
CD19CAR T cells facilitate a transformational treatment in various relapsed and refractory aggressive B-lineage cancers. In general, encouraging response rates have been observed B-lineage-derived non-Hodgkin’s lymphomas treated with cells. The major cause of death heavily pretreated NHL patients is lymphoma progression recurrence. Inefficient CAR cell therapy the result limited potency product or due to loss targeted antigen. Target antigen has identified as key factor that can be addressed...
We developed a bioinformatics-led substrate discovery workflow to expand the known repertoire of MALT1. Our approach, termed GO-2-Substrates, integrates protein function information, including GO terms from substrates, with sequences rank candidates by similarity. applied GO-2-Substrates MALT1, paracaspase and master regulator NF-κB signalling in adaptive immune responses. With only 12 evolutionarily conserved functions phenotypes Malt1-/- mice strongly implicate existence undiscovered...
Haploidentical stem cell transplantation (haplo SCT) in Stage IV neuroblastoma relapsed patients has been proven efficacious, while immunotherapy utilizing the anti-GD2 antibody dinutuximab beta become a standard treatment for neuroblastoma. The combinatorial therapy of haplo SCT and may potentiate efficacy immunotherapy. To gain further understanding synergistic effects, functional immunomonitoring was assessed during clinical trial CH14.18 1021 Antibody IL2 After Children with Relapsed...
Osteosarcoma is a malignant bone tumor with very limited therapeutic options ([ 1 ][1]). However, targeting the frequently overexpressed disialoganglioside GD2 was successful in preclinical studies bispecific antibodies 2 ][2]), and clinical trial ongoing using clinically
BACKGROUND: Aortic stenosis (AS) is driven by progressive inflammatory and fibrocalcific processes regulated circulating valve resident endothelial interstitial cells. The impact of platelets, platelet-derived mediators, platelet-monocyte interactions on the acceleration local valvular inflammation mineralization presently unknown. METHODS: We prospectively enrolled 475 consecutive patients with severe symptomatic AS undergoing aortic replacement. Clinical workup included repetitive...
Pituitary neuroendocrine tumors (PitNET) are among the most common intracranial tumors. Despite a frequent benign course, aggressive behavior can occur. Tumor is known to be under influence of tumor microenvironment (TME). However, relationship between TME cells and has not been adequately explored in PitNET. We performed differential expression analysis as well gene program identification based on single-cell RNA sequencing comparatively characterize transcriptome seven gonadotroph three...
Abstract BACKGROUND A major challenge in the treatment of brain tumors is limited penetration many drugs through blood-brain barrier (BBB). BBB characteristics include endothelial cells connected by tight junction proteins (e.g. Claudin5, ZO1, occludin) and expression efflux transporters P-gp) with physiological role to limit accumulation potentially toxic substances tissue. Our study aims enhance our understanding composition across different molecular groups ependymoma (EPN) goal...
Abstract Increasing evidence highlights the diverse functions of extracellular vesicles (EVs) as intercellular messengers in all facets cancer progression, pointing towards a potential new avenue treatment. Limited understanding tumor-specific deregulations and lack suitable drug compounds have hampered clinical translation targeted interference with EV signaling. The most aggressive types intracranial ependymoma (EPN) children adults are resistant to chemotherapy. Despite enormous...
Abstract BACKGROUND Aggressive ependymoma (EPN) exhibit primary and secondary radio- chemotherapy resistance with the poorest prognosis in pediatric groups PF-EPN-A ST-EPN-ZFTA. Recently, tumor cell networks formed by membrane protrusions, such as tunneling nanotubes (TNT) or microtubes (TM), have been identified other glial brain tumors. These structures facilitate intercellular hierarchical Ca2+-communication contribute to therapy resistance. Previous data from our group suggested...
Abstract Chimeric antigen receptor (CAR)-T therapy holds great promise to sustainably improve cancer treatment. However, currently, a broad applicability of CAR-T cell therapies is hampered by limited versatility and tractability the lack exclusive target antigens discriminate cancerous from healthy tissues. To achieve temporal qualitative control on function, we engineered Adapter CAR (AdCAR) system. AdCAR-T are redirected surface via biotin-labeled adapter molecules in context specific...
<title>Abstract</title> Targeting AML by chimeric antigen receptor T cells (CAR-T) has been challenging due to the promiscuous expression of AML-associated antigens on healthy hematopoietic stem and progenitor as well a high degree inter- intratumoral heterogeneity. Consequently, we did not yet see dramatic clinical successes, in B-phenotypic malignancies treated with CD19- or BCMA-directed CAR-T cells. In present study, analyzed heterogeneity 30 primary pediatric samples at single-cell...