A5085953389- Multiple Myeloma Research and Treatments
- Protein Degradation and Inhibitors
- CAR-T cell therapy research
- Melanoma and MAPK Pathways
- Peptidase Inhibition and Analysis
- Monoclonal and Polyclonal Antibodies Research
- Chemokine receptors and signaling
- Chronic Lymphocytic Leukemia Research
- Cancer Genomics and Diagnostics
- Cancer Mechanisms and Therapy
- Cancer Treatment and Pharmacology
- Viral Infectious Diseases and Gene Expression in Insects
- Histone Deacetylase Inhibitors Research
- Immune Cell Function and Interaction
- Ubiquitin and proteasome pathways
- Extracellular vesicles in disease
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Acute Lymphoblastic Leukemia research
- Immunotherapy and Immune Responses
- Colorectal Cancer Treatments and Studies
- Sarcoma Diagnosis and Treatment
- Acute Myeloid Leukemia Research
- T-cell and B-cell Immunology
- HIV/AIDS drug development and treatment
Comprehensive Cancer Center Mainfranken
2024-2025
Universitätsklinikum Würzburg
2023-2025
Dana-Farber Cancer Institute
2018-2025
University Medical Center Freiburg
2013-2024
University of Freiburg
2013-2024
Harvard University
2018-2023
Broad Institute
2019-2023
Zusammenfassung Die medikamentöse Tumortherapie entwickelt sich von der klassischen zytotoxischen Chemotherapie hin zu immer gezielteren Immuntherapien. Im Gegensatz monoklonalen Antikörpern richten bispezifische Antikörper (BsAb) gegen 2 unterschiedliche Antigene und können auf diese Weise entweder Immuneffektorzellen mit Tumorzellen verbinden oder Signalwege in blockieren. Bisher wurden mehrere BsAb zur Behandlung hämatologischer Neoplasien ausgewählter solider Tumoren zugelassen....
Summary Cell adhesion‐mediated drug resistance ( CAM ‐ DR ) by the bone marrow BM is fundamental to multiple myeloma MM propagation and survival. Targeting protection increase efficacy of current anti‐myeloma treatment has not been extensively pursued. To extend understanding , we hypothesized that cytotoxic effects novel agents may be abrogated presence stroma cells BMSC s) restored addition CXCL 12 antagonist NOX ‐A12 or CXCR 4 inhibitor plerixafor. Following this hypothesis, evaluated...
Efficacy and durability remain central shortcomings of T-cell based therapies in multiple myeloma (MM). Here, we employ blood-based transcriptional profiling to define impaired fitness as putative biomarker associated with sensitivity PD1 inhibition CAR-T refractory MM patients.
Additional malignancies in multiple myeloma patients after first-line and maintenance treatment have been observed, questioning whether specific risks exist. Second primary also gained attention since randomized data showed associations to newer drugs. We conducted this large registry analysis 744 consecutive analyzed: 1) frequency onset of additional malignancies; 2) second malignancy- myeloma-specific risks. assessed the terms host-, myeloma- treatment-specific characteristics. To compare...
Local ablative therapies (LAT) are increasingly used in patients with metastatic soft tissue sarcoma (STS), yet evidence-based standards lacking. This study aimed to assess the impact of LAT on survival STS and identify prognostic factors.
Despite considerable advances, multiple myeloma (MM) remains incurable and the development of novel therapies targeting interplay between plasma cells (PCs) their bone marrow (BM) microenvironment essential. We investigated effect various agents in vitro on proliferation, phenotype, morphology, actin polymerization migration MM and, vivo, tumour growth L363-bearing non-obese diabetic severe combined immunodeficient mice with a deficient interleukin-2 receptor gamma chain (NSG). In vitro, we...
Abstract Purpose: Although remarkably effective in some patients, precision medicine typically induces only transient responses despite initial absence of resistance-conferring mutations. Using BRAF-mutated myeloma as a model for resistance to we investigated if cancer cells have the ability ensure their survival by rapidly adapting BRAF inhibitor treatment. Experimental Design: Full-length single-cell RNA (scRNA) sequencing (scRNA-seq) was conducted on 3 patients with and 1 healthy donor....
Abstract Patients with corticosteroid-refractory acute graft-versus-host disease (aGVHD) have a low one-year survival rate. Identification and validation of novel targetable kinases in patients who experience corticosteroid-refractory-aGVHD may help improve outcomes. Kinase-specific proteomics leukocytes from corticosteroid-refractory-GVHD identified rho kinase type 1 (ROCK1) as the most significantly upregulated kinase. ROCK1/2 inhibition improved histological GVHD severity mice was...
Dedifferentiated liposarcoma (DDLPS) is a rare mesenchymal cancer originating from the adipose tissue, with poor survival rates for most patients, highlighting critical need novel treatment options. This report examines efficacy and safety of sequential pre-treatment marine-derived alkaloid trabectedin followed by checkpoint inhibition using anti-PD-1 antibody nivolumab in 63-year-old male patient unresectable retroperitoneal DDLPS. Treatment was initiated at time seventh relapse as part...
Abstract The definition of high‐risk (HR) multiple myeloma (MM) is still a matter debate. We prospectively evaluated the HR detection using FISH in combination with SKY92 gene expression profiling 258 MM patients (newly diagnosed [ND] MM: n = 109; relapsed/refractory [RR] 149). was significantly enriched RRMM (57/121, 47.1%) compared NDMM (17/95, 17.9%) ( p < 0.0001). showed shorter progression‐free survival (PFS) 0.0001) and overall (OS) than standard‐risk (SR). In NDMM, also indicated...
<title>Abstract</title> Extramedullary multiple myeloma (EMD) is associated with low response rates, short progression-free survival and poor prognosis. CAR T cells bispecific antibodies (bsABs) have shown efficacy in relapsed but it remains uncertain whether one cell redirection strategy should be preferred. We retrospectively analyzed 80 patients EMD not adjacent to the bone treated ide-cel, cilta-cel, teclistamab or talquetamab at three academic centers Germany. All were heavily...
Abstract Background: Even with considerable advancements in multiple myeloma (MM) therapy, proteasome inhibitors (PIs) continue to be an indispensable treatment pillar MM. However, the development of PI resistance remains a significant clinical challenge. Previous studies proposed different causes contributing PI-resistance, though, these mechanisms explain only subset cases. Hence, we employed multi-omics approach identify further molecular pathways underlying Methods: We applied proteomic...
Abstract Background: The treatment landscape in Multiple Myeloma (MM) shifts towards immunotherapies with the G protein-coupled receptor class C group 5 member D (GPRC5D) as a promising antigen for T cell engagers (TCE) and investigational CART constructs. Monoallelic genetic alterations GPRC5D are present up to 15% of MM patients prior directed therapy. incidence acquired biallelic events following has be determined. Recently, loss was identified underlying mechanism resistance toward...
<title>Abstract</title> Accurate prediction of risk progression from smoldering (SMM) to active multiple myeloma (MM) is paramount individualized early therapeutic strategies with minimum overtreatment. Current stratification models do not account for evolving biomarker trajectories. We assembled the largest cohort date 2,270 SMM patients six international centers longitudinal clinical and biological data train validate PANGEA 2.0 models. Four biomarkers were significantly associated shorter...
Belantamab mafodotin (belantamab) is a first-in-class anti-BCMA antibody-drug conjugate approved for the treatment of triple-class refractory multiple myeloma. It provides unique therapeutic option patients ineligible CAR-T and bispecific antibody therapy, and/or progressing on anti-CD38 where bispecifics might be kept in reserve. Wider use drug can challenged by its distinct ocular side effect profile, including corneal microcysts keratopathy. While dose reduction has been most effective...