A5080836916- Multiple Myeloma Research and Treatments
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Monoclonal and Polyclonal Antibodies Research
- Peptidase Inhibition and Analysis
- Hematopoietic Stem Cell Transplantation
- Synthesis and Biological Evaluation
- Chronic Lymphocytic Leukemia Research
- Protein Degradation and Inhibitors
- Calcium signaling and nucleotide metabolism
- RNA Interference and Gene Delivery
- Lymphoma Diagnosis and Treatment
- Glycosylation and Glycoproteins Research
- Cancer therapeutics and mechanisms
- Chemokine receptors and signaling
- Cancer Immunotherapy and Biomarkers
- vaccines and immunoinformatics approaches
- Quinazolinone synthesis and applications
- Viral Infectious Diseases and Gene Expression in Insects
- Nanowire Synthesis and Applications
- Celiac Disease Research and Management
- Ocular Diseases and Behçet’s Syndrome
- Virus-based gene therapy research
Amsterdam University Medical Centers
2019-2025
Vrije Universiteit Amsterdam
2019-2025
Amsterdam UMC Location Vrije Universiteit Amsterdam
2015-2025
Cancer Center Amsterdam
2018-2025
BD Biosciences (United States)
2024
University Medical Center
2014-2020
University Hospital and Clinics
2014-2020
University Medical Center Utrecht
2008-2019
Peking University
2019
Peking University People's Hospital
2019
Abstract CD38, a type II transmembrane glycoprotein highly expressed in hematological malignancies including multiple myeloma (MM), represents promising target for mAb-based immunotherapy. In this study, we describe the cytotoxic mechanisms of action daratumumab, novel, high-affinity, therapeutic human mAb against unique CD38 epitope. Daratumumab induced potent Ab-dependent cellular cytotoxicity CD38-expressing lymphoma- and MM-derived cell lines as well patient MM cells, both with...
Daratumumab (DARA) is a human CD38-specific IgG1 antibody that in clinical development for the treatment of multiple myeloma (MM). The potential antibodies to induce macrophage-mediated phagocytosis, combination with known presence macrophages tumor microenvironment MM and other hematological tumors, led us investigate contribution antibody-dependent, phagocytosis DARA's mechanism action. Live cell imaging revealed DARA efficiently induced which individual rapidly sequentially engulfed...
Donor lymphocyte infusion (DLI) into patients with a relapse of their leukemia or multiple myeloma after allogeneic stem cell transplantation (alloSCT) has been shown to be successful treatment approach. The hematopoiesis-restricted minor histocompatibility antigens (mHAgs) HA-1 HA-2 expressed on malignant cells the recipient may serve as target for alloreactive donor T cells. Recently we treated three mHAg HA-1- and/or HA-2-positive disease alloSCT DLI from HA-2-negative donors. Using...
Daratumumab is an anti-CD38 monoclonal antibody with lytic activity against multiple myeloma (MM) cells, including ADCC (antibody-dependent cellular cytotoxicity) and CDC (complement-dependent cytotoxicity). Owing to a marked heterogeneity of response daratumumab therapy in MM, we investigated determinants the sensitivity MM cells toward daratumumab-mediated CDC. In bone marrow samples from 144 patients, observed no difference lysis between newly diagnosed or relapsed/refractory patients....
Targeting nonspecific, tumor-associated antigens (TAA) with chimeric antigen receptors (CAR) requires specific attention to restrict possible detrimental on-target/off-tumor effects. A reduced affinity may direct CAR-engineered T (CAR-T) cells tumor expressing high TAA levels while sparing low normal tissues. However, decreasing the of CAR-target binding compromise overall antitumor Here, we demonstrate prime importance type intracellular signaling on function low-affinity CAR-T cells.We...
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...
Abstract For vaccination strategies and adoptive immunotherapy purposes, immature dendritic cells (DC) can be generated from adherent monocytes using GM-CSF IL-4. Presently, the only clinically applicable method to induce stable maturation of DC is use supernatants activated (monocyte-conditioned medium (MCM)). MCM contains an undefined mixture cytokines difficult standardize. Here we report that simply induced by addition polyriboinosinic polyribocytidylic acid (poly(I:C)), a synthetic...
Celiac disease is a common severe intestinal resulting from intolerance to dietary wheat gluten and related proteins. The large majority of patients expresses the HLA-DQ2 and/or DQ8 molecules, gluten-specific HLA-DQ-restricted T cells have been found at site lesion in gut. nature peptides that are recognized by such cells, however, has unclear so far. We now report identification gliadin-derived epitope dominantly HLA-DQ8-restricted cells. characterization epitopes key step toward...
Background In our efforts to develop novel effective treatment regimens for multiple myeloma we evaluated the potential benefits of combining immunomodulatory drug lenalidomide with daratumumab. Daratumumab is a human CD38 monoclonal antibody which kills CD38+ cells via antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity and apoptosis.Design Methods To explore effect combined daratumumab, first carried out standard assays in cell line UM-9 primary isolated from...
Adoptive transfer of chimeric antigen receptor-transduced T cells is a promising strategy for cancer immunotherapy. The CD38 molecule, with its high expression on multiple myeloma cells, appears suitable target antibody therapy. Prompted by this, we used three different sequences to generate second-generation retroviral CD38-chimeric receptor constructs which transduced from healthy donors and patients. We then evaluated the preclinical efficacy safety cells. Irrespective donor sequence,...
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.
Novel therapeutic agents have significantly improved the survival of patients with multiple myeloma. Nonetheless, prognosis myeloma who become refractory to novel lenalidomide and bortezomib is very poor, indicating urgent need for new options these patients. The human CD38 monoclonal antibody daratumumab being evaluated as a therapy Prompted encouraging results ongoing clinical phase I/II trials, we now addressed potential value alone or in combination treatment lenalidomide-...
Abstract Daratumumab is a CD38‐targeted human monoclonal antibody with direct anti‐myeloma cell mechanisms of action. Flow cytometry in relapsed and/or refractory multiple myeloma (RRMM) patients treated daratumumab revealed cytotoxic T‐cell expansion and reduction immune‐suppressive populations, suggesting immune modulation as an additional mechanism Here, we performed in‐depth analysis the effects on immune‐cell subpopulations using high‐dimensional mass cytometry. Whole‐blood bone‐marrow...
Birdshot chorioretinopathy (BSCR) is a rare form of autoimmune uveitis that can lead to severe visual impairment. Intriguingly, >95% cases carry the HLA-A29 allele, which defines strongest documented HLA association for human disease. We have conducted genome-wide study in 96 Dutch and 27 Spanish cases, 398 unrelated 380 controls. Fine-mapping primary MHC through high-resolution imputation at classical loci, identified HLA-A*29:02 as principal (odds ratio (OR) = 157.5, 95% CI 91.6–272.6, P...