A5040169496- Virus-based gene therapy research
- CAR-T cell therapy research
- Cancer Research and Treatments
- Immunotherapy and Immune Responses
- Sarcoma Diagnosis and Treatment
- Viral Infectious Diseases and Gene Expression in Insects
- Immune Cell Function and Interaction
- Biochemical and Molecular Research
- Cancer Immunotherapy and Biomarkers
- Neuroblastoma Research and Treatments
- Extracellular vesicles in disease
- Hematopoietic Stem Cell Transplantation
- Cancer-related molecular mechanisms research
- Heat shock proteins research
- RNA Research and Splicing
- T-cell and B-cell Immunology
- vaccines and immunoinformatics approaches
- Ovarian cancer diagnosis and treatment
- Monoclonal and Polyclonal Antibodies Research
- Urinary Bladder and Prostate Research
- Urinary Tract Infections Management
- Cardiac Imaging and Diagnostics
- Testicular diseases and treatments
- Cell Adhesion Molecules Research
- Urinary and Genital Oncology Studies
München Klinik Schwabing
2011-2024
Technical University of Munich
2015-2024
Children's Cancer Center
2021
German Marine Research Consortium
2021
Deutschen Konsortium für Translationale Krebsforschung
2021
Cancer Research Center
2021
Klinikum rechts der Isar
2011-2017
German Cancer Research Center
2016
München Klinik
2016
Helmholtz Zentrum München
2011
Ewing tumors comprise the second most common type of bone-associated cancer in children and are characterized by oncogenic EWS/FLI1 fusion proteins early metastasis. Compelling evidence suggests that elevated levels intracellular oxidative stress contribute to enhanced aggressiveness numerous cancers, possibly including tumors. Using comprehensive microarray analyses RNA interference, we identified six-transmembrane epithelial antigen prostate 1 (STEAP1)-a membrane-bound mesenchymal stem...
Urinary bladder malformations associated with outlet obstruction are a frequent cause of progressive renal failure in children. We here describe muscarinic acetylcholine receptor M3 (CHRM3) (1q41-q44) homozygous frameshift mutation familial congenital malformation prune-belly-like syndrome, defining an isolated gene defect underlying this sometimes devastating disease. CHRM3 encodes the receptor, which we show is present developing epithelia and muscle. These observations may imply that has...
Exosomes are small RNA- and protein-containing extracellular vesicles (EVs) that thought to mediate hetero- homotypic intercellular communication between normal malignant cells.Tumour-derived exosomes believed promote re-programming of the tumour-associated stroma favour tumour growth metastasis. Currently, have been intensively studied in carcinomas. However, little is known about their existence possible role sarcomas. Here, we report on identification with exosomal features derived from...
Aberrant expression of ETS transcription factors characterizes numerous human malignancies. Many these proteins, including EWS::FLI1 and EWS::ERG fusions in Ewing sarcoma (EwS) TMPRSS2::ERG prostate cancer (PCa), drive oncogenic programs via binding to GGAA repeats. We report here that both ERG bind transcriptionally activate GGAA-rich pericentromeric heterochromatin. The respective pathogen-like HSAT2 HSAT3 RNAs, together with LINE, SINE, ERV other repeat transcripts, are expressed EwS PCa...
Abstract Purpose: Ewing sarcoma (EwS) is a highly malignant pediatric tumor characterized by non-T-cell-inflamed immune-evasive phenotype. When relapsed or metastasized, survival poor, emphasizing the need for novel treatment strategies. Here, we analyze combination approach using YB-1-driven oncolytic adenovirus XVir-N-31 and CDK4/6 inhibition to augment EwS immunogenicity. Experimental Design: In vitro, viral toxicity, replication, immunogenicity were studied in several cell lines. vivo...
Pregnancy-associated plasma protein-A (PAPPA), also known as pappalysin, is a member of the insulin-like growth factor (IGF) family. PAPPA acts protease, cleaving IGF inhibitors, i.e., binding proteins (IGFBPs), thereby setting free IGFs. The insulin/IGF-axis involved in cancer general and Ewing sarcoma (ES) particular. ES highly malignant bone tumor characterized by early metastatic spread. associated with various cancers. It overexpressed required for proliferation ES. stimulates normal...
In this study we report the functional comparison of T cell receptor (TCR)-engineered major histocompatibility complex (MHC) class I-restricted CD4+ versus CD8+ cells targeting a peptide from six transmembrane epithelial antigen prostate 1 (STEAP1) in context HLA-A*02:01. STEAP1 is tumor-associated antigen, which overexpressed many cancers, including Ewing sarcoma (EwS). Based on previous observations, postulated strong antitumor potential tumor-redirected transduced with an HLA TCR against...
Journal Article Myocardial Thallium201imaging in hypertrophic obstructive cardiomyopathy Get access P. HANRATH, HANRATH *Department of Cardiology, University Hospital Hamburg-EppendorfWest Germany Request for reprints to: Peter Hanrath, M.D., Department Hamburg-Eppendorf, Martinistraβe 52, D-2000 Hamburg 20, West Search other works by this author on: Oxford Academic PubMed Google Scholar D. MATHEY, MATHEY R. MONTZ, MONTZ †Nuclear Medicine, U. THIEL, THIEL H. VORBRINGER, VORBRINGER W. KUPPER,...
Pediatric cancers, including Ewing sarcoma (ES), are only weakly immunogenic and the tumor-patients' immune system often is devoid of effector T cells for tumor elimination. Based on expression profiling technology, targetable tumor-associated antigens (TAA) identified exploited engineered T-cell therapy. Here, specific recognition lytic potential transgenic allo-restricted CD8+ cells, directed against ES-associated antigen 6-transmembrane epithelial prostate 1 (STEAP1), was examined....
Ewing sarcoma (EwS) is an aggressive pediatric cancer of bone and soft tissues characterized by scant T cell infiltration predominance immunosuppressive myeloid cells. Given the important roles extracellular vesicles (EVs) in cancer-host crosstalk, we hypothesized that EVs secreted EwS tumors target cells promote phenotypes. Here, were purified from fibroblast lines exhibited characteristics small EVs, including size (100-170 nm) exosome markers CD63, CD81, TSG101. Treatment healthy...
The development of a successful immunotherapy is hampered by an ineffective T-cell repertoire against tumour antigens and the inability patient's immune system to overcome tolerance-inducing mechanisms. Here, we test specific recognition lytical potential allo-restricted CD8+ T cells Ewing (ET) associated Enhancer Zeste, Drosophila Homolog 2 (EZH2), Chondromodulin-I (CHM1) identified through previous microarray analysis. Following repetitive CHM1319 (VIMPCSWWV) EZH2666 (YMCSFLFNL)...
// Franziska Blaeschke 1, 10, * , Uwe Thiel Andreas Kirschner 1 Melanie Thiede Rebeca Alba Rubio 2 David Schirmer Thomas Kirchner 2, 3, 4 Günther H.S. Richter Sabine Mall 5 Richard Klar Stanley Riddell 6 Dirk H. Busch 7, 8 Angela Krackhardt G.P. Grunewald Stefan Burdach 9 Laboratory for Functional Genomics and Transplantation Biology, Department of Pediatrics Children's Cancer Research Center, Klinikum rechts der Isar, Technische Universitaet Muenchen, Munich, Germany Pediatric Sarcoma...
Background Ewing sarcoma (EwS) is an aggressive and highly metastatic bone soft tissue tumor in pediatric patients young adults. Cure rates are low when present with or relapsed disease. Therefore, innovative therapy approaches urgently needed. Cellular- oncolytic virus-based immunotherapies on the rise for solid cancers. Methods Here, we assess combination of EwS tumor-associated antigen CHM1 319 -specific TCR-transgenic CD8 + T cells YB-1-driven (i.e. E1A13S-deleted) adenovirus XVir-N-31...
Allogeneic haematopoietic stem cell transplantation (allo-SCT) may provide donor cytotoxic T cell-/NK cell-mediated disease control in patients with rhabdomyosarcoma (RMS). However, little is known about the prevalence of graft-vs-RMS effects and only a few case experiences have been reported. We evaluated allo-SCT outcomes 30 European Group for Blood Marrow Transplantation (EBMT)-registered advanced RMS regarding toxicity, progression-free survival (PFS) overall (OS) after allo-SCT. Twenty...
Background: Chondromodulin-I (CHM1) sustains malignancy in Ewing sarcoma (ES). Refractory ES carries a dismal prognosis and patients with bone marrow (BM) metastases do not survive irrespective of therapy. We assessed HLA-A*02:01/CHM1-specific allorestricted T cell receptor (TCR) wild-type transgenic cytotoxic (CD8+) cells against ES.Patients Methods: Three refractory HLA-A2+ were treated HLA-A*02:01/peptide-specific allorepertoire-derived (i.e., allorestricted) CD8+ cells. Patient #1...
// Uwe Thiel 1 , Angela Wawer Irene von Luettichau Hans-Ulrich Bender Franziska Blaeschke ,Thomas G.P. Grunewald 2 Marc Steinborn 3 Barbara Röper 4, 10, * Halvard Bonig 5, 6 Thomas Klingebiel 5 Peter Bader Ewa Koscielniak 7 Michael Paulussen 8 Uta Dirksen 9 Heribert Juergens Hans-Jochem Kolb Stefan E.G. Burdach 1, 10 Department of Pediatrics and Pediatric Oncology Center, Kinderklinik München Schwabing, Städtisches Klinikum und rechts der Isar, Wilhelm Sander Sarcoma Unit, Technische...
Immunotherapy can revolutionize anti-cancer therapy if specific targets are available. Immunogenic peptides encoded by cancer-specific genes (CSGs) may enable targeted immunotherapy, even of oligo-mutated cancers, which lack neo-antigens generated protein-coding missense mutations. Here, we describe an algorithm and user-friendly software named RAVEN (Rich Analysis Variable gene Expressions in Numerous tissues) that automatizes the systematic fast identification CSG-encoded highly affine to...
SUMMARY Ewing sarcoma (EwS) is an aggressive childhood malignancy with a high propensity for metastasis. By analyzing cohorts of patients and age-matched healthy donors, we establish that EwS metastatic progression accompanied by elevated plasma levels multiple proinflammatory cytokines, interferons extracellular vesicles (EVs). The latter were enriched transcripts derived from LINE, SINE ERV retroelements locus-specific pericentromeric regions, including HSAT2. We show some these RNAs,...
Cancer cells are in most instances characterized by rapid proliferation and uncontrolled cell division. Hence, they must adapt to proliferation-induced metabolic stress through intrinsic or acquired antimetabolic responses maintain homeostasis survival. One mechanism achieve this is reprogramming gene expression a metabolism-dependent manner. MondoA (also known as Myc-associated factor X-like protein X-interacting [MLXIP]), member of the MYC interactome, has been described an example such...
Allogeneic stem cell transplantation (allo-SCT) and donor lymphocyte infusions (DLI) may induce a graft-versus-tumor effect in pediatric sarcoma patients. Here, we describe general feasibility, toxicity efficacy of DLI after allo-SCT.4 8 patients responded. ES#4 had stable disease (SD) for 9 months RMS#4 partial response with combined hyperthermia/chemotherapy. In ES#4, led to SD 6 reverted residual before allo-SCT into complete remission. After DLI, developed acute GvHD (°III-°IV), also...
// Andreas Kirschner 1 , Melanie Thiede Franziska Blaeschke 1, 2 Günther H.S. Richter Julia S. Gerke 3 Michaela C. Baldauf Thomas G.P. Grünewald 3, 4, 5 Dirk H. Busch 6 Stefan Burdach * Uwe Thiel Laboratory for Functional Genomics and Transplantation Biology, Departments of Pediatrics Children’s Cancer Research Center, Klinikum rechts der Isar, Technische Universität München, Munich, Germany Immunotherapy, Dr. von Hauner Hospital, Medical center the LMU Pediatric...
Abstract Patients with advanced Ewing sarcoma (AES) carry a poor prognosis. Retrospectively, we analyzed 66 AES patients treated allogeneic stem cell transplantation (allo-SCT) receiving HLA-mismatched (group A, n = 39) versus HLA-matched grafts B, 27). Median age at diagnosis was 13 years, and 15 years (range 3–49 years) allo-SCT. The two groups did not differ statistically in distribution of gender, age, remission status/number relapses allo-SCT, or risk stratum. 9/39 (23%) group A 2/27...