A5055428904- Multiple Myeloma Research and Treatments
- Peptidase Inhibition and Analysis
- Monoclonal and Polyclonal Antibodies Research
- Synthesis and Biological Evaluation
- Calcium signaling and nucleotide metabolism
- Quinazolinone synthesis and applications
- Neuroblastoma Research and Treatments
- Immune Cell Function and Interaction
- Protein Degradation and Inhibitors
- Cancer, Hypoxia, and Metabolism
- Chronic Lymphocytic Leukemia Research
- CAR-T cell therapy research
- T-cell and B-cell Immunology
- Angiogenesis and VEGF in Cancer
- Vascular Malformations and Hemangiomas
- Hippo pathway signaling and YAP/TAZ
- Adrenal and Paraganglionic Tumors
- Vascular Tumors and Angiosarcomas
- Signaling Pathways in Disease
- Ubiquitin and proteasome pathways
- Genomics and Chromatin Dynamics
Vrije Universiteit Amsterdam
2019-2024
Amsterdam University Medical Centers
2019-2024
BD Biosciences (United States)
2024
Cancer Center Amsterdam
2023
University of Amsterdam
2012-2019
Amsterdam UMC Location Vrije Universiteit Amsterdam
2017-2018
Amsterdam UMC Location University of Amsterdam
2009-2017
Neuroblastoma is a pediatric tumor of the sympathetic nervous system. MYCN (V-myc myelocytomatosis viral-related oncogene, neuroblastoma derived [avian]) amplified in 20% neuroblastomas, and these tumors carry poor prognosis. However, without amplification also may have outcome. Here, we identified downstream targets by shRNA-mediated silencing cells. From targets, 157 genes showed an expression profile correlating with mRNA levels NB88, series 88 tumors, therefore represent vivo relevant...
Abstract Transition between differentiation states in development occurs swift but the mechanisms leading to epigenetic and transcriptional reprogramming are poorly understood. The pediatric cancer neuroblastoma includes adrenergic (ADRN) mesenchymal (MES) tumor cell types, which differ phenotype, super-enhancers (SEs) core regulatory circuitries. These types can spontaneously interconvert, mechanism remains largely unknown. Here, we unravel how a NOTCH3 intracellular domain reprogrammed...
Abstract Cell surface expression levels of GPRC5D, an orphan G protein–coupled receptor, are significantly higher on multiple myeloma (MM) cells, compared with normal plasma cells or other immune which renders it a promising target for immunotherapeutic strategies. The novel GPRC5D-targeting T-cell redirecting bispecific antibody, talquetamab, effectively kills GPRC5D+ MM cell lines in the presence T from both healthy donors heavily pretreated patients. In addition, talquetamab has potent...
Daratumumab treatment results in a marked reduction of CD38 expression on multiple myeloma cells. The aim this study was to investigate the clinical implications and underlying mechanisms daratumumab-mediated reduction.
Abstract Purpose: Multiple myeloma (MM) patients with disease refractory to all available drugs have a poor outcome, indicating the need for new agents novel mechanisms of action. Experimental Design: We evaluated anti-MM activity fully human BCMA×CD3 bispecific antibody JNJ-7957 in cell lines and bone marrow (BM) samples. The impact several tumor- host-related factors on sensitivity therapy was also evaluated. Results: show that has potent against 4 MM lines, tumor cells 48 49 BM samples...
The CD38-targeting antibody daratumumab has marked activity in multiple myeloma (MM). Natural killer (NK) cells play an important role during therapy by mediating antibody-dependent cellular cytotoxicity via their FcγRIII receptor (CD16), but they are also rapidly decreased following initiation of treatment. We characterized the NK cell phenotype at baseline and monotherapy flow cytometry time flight to assess its impact on response development resistance (DARA-ATRA study; NCT02751255). At...
Abstract Purpose: Bispecific antibodies (BsAb) directed against B-cell maturation antigen (teclistamab) or the orphan G protein-coupled receptor GPRC5D (talquetamab) induce deep and durable responses in heavily pretreated patients with multiple myeloma. However, mechanisms underlying primary acquired resistance remain poorly understood. Experimental Design: The anti–multiple myeloma activity of teclistamab talquetamab was evaluated bone marrow (BM) samples from T-cell phenotype function were...
The CD38-targeting antibody daratumumab mediates its anti-myeloma activities not only through Fc-receptor-dependent effector mechanisms, but also by effects on T-cell immunity depletion of CD38+ regulatory T-cells, B-cells, and myeloid-derived suppressor cells. Therefore, combining with modulators other potent immune inhibitory pathways, such as the PD-1/PD-L1 axis, may further improve efficacy. We show that multiple myeloma (MM) cells from relapsed/refractory patients have increased...
// Christie P.M. Verkleij 1 , * Kristine A. Frerichs Marloes Broekmans Saida Absalah Patricia W.C. Maas-Bosman Sandy Kruyswijk Inger S. Nijhof Tuna Mutis Sonja Zweegman and Niels W.C.J. van de Donk Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Hematology, The Netherlands Shared first authors Correspondence to: Donk, email: n.vandedonk@vumc.nl Keywords: multiple myeloma; bispecific antibody; immunotherapy; BCMA; CD38 Received: October 09, 2020 Accepted: 13, Published: November...
Nine commercially available vascular endothelial growth factor (VEGF) antibodies were investigated for their ability to immunostain malformations (VMs) with or without immature capillary proliferation. First, all optimized performance in IHC, placenta and colon adenocarcinoma as positive control tissues. Five regarded unfit VEGF immunostaining based on poor criteria. Subsequently, Western blot analysis using rabbit polyclonal antibody (Thermo RB-9031) revealed a clear 45-kDa band tissue...
<div>AbstractPurpose:<p>Bispecific antibodies (BsAb) directed against B-cell maturation antigen (teclistamab) or the orphan G protein-coupled receptor GPRC5D (talquetamab) induce deep and durable responses in heavily pretreated patients with multiple myeloma. However, mechanisms underlying primary acquired resistance remain poorly understood.</p>Experimental Design:<p>The anti–multiple myeloma activity of teclistamab talquetamab was evaluated bone marrow (BM) samples...
<p>Supplemental Tables S1-S3, Figures S1-S15</p>
<p>Supplemental Tables S1-S3, Figures S1-S15</p>
<div>AbstractPurpose:<p>Bispecific antibodies (BsAb) directed against B-cell maturation antigen (teclistamab) or the orphan G protein-coupled receptor GPRC5D (talquetamab) induce deep and durable responses in heavily pretreated patients with multiple myeloma. However, mechanisms underlying primary acquired resistance remain poorly understood.</p>Experimental Design:<p>The anti–multiple myeloma activity of teclistamab talquetamab was evaluated bone marrow (BM) samples...
Abstract Most high stage neuroblastoma initially respond to chemotherapy, but ultimately relapse as therapy-resistant tumor. The mechanisms driving and resistance remain elusive. We observed that new cell lines cultured in defined medium always include two phenotypically divergent types. Whole genome sequencing showed both types were genetically identical. One type has a neuro-epithelial (NE) phenotype expresses all classical diagnostically used markers. other mesenchymal (MES) character,...
<p>Monocytes take up AF488-labeled daratumumab-CD38 complexes from PKH-26-stained UM9 cells.</p>
<p>Daratumumab is transferred from UM9 cells to monocytes.</p>
<p>Daratumumab-mediated CD38 reduction of MM cells in the presence PBMCs as shown by Western blot analysis.</p>
<p>Supplemental Methods, Supplementary Tables, Figure Legends</p>