A5007462898- Immune Cell Function and Interaction
- CAR-T cell therapy research
- Hematopoietic Stem Cell Transplantation
- T-cell and B-cell Immunology
- Virus-based gene therapy research
- Cytomegalovirus and herpesvirus research
- Immunotherapy and Immune Responses
- Acute Lymphoblastic Leukemia research
- Autoimmune and Inflammatory Disorders Research
- Hemoglobinopathies and Related Disorders
- Immune cells in cancer
- Immunodeficiency and Autoimmune Disorders
- Monoclonal and Polyclonal Antibodies Research
- Systemic Lupus Erythematosus Research
- Sarcoma Diagnosis and Treatment
- Acute Myeloid Leukemia Research
- Viral Infectious Diseases and Gene Expression in Insects
- Viral gastroenteritis research and epidemiology
- IL-33, ST2, and ILC Pathways
- Chronic Lymphocytic Leukemia Research
- Cancer Immunotherapy and Biomarkers
- Cytokine Signaling Pathways and Interactions
- Congenital heart defects research
- interferon and immune responses
- RNA Interference and Gene Delivery
Leiden University Medical Center
2016-2025
Leiden University
1997-2024
Willem-Alexander Kinderziekenhuis
2023
Institut Català d'Oncologia
2011
Royal University Hospital
2011
Istituto Ortopedico Rizzoli
2011
Pediatrics and Genetics
2006-2010
Northwestern University
2003
Utrecht University
1997-1998
Amsterdam UMC Location University of Amsterdam
1998
Glioblastoma multiforme (GBM) is the most common primary brain tumor and without exception lethal. GBMs modify immune system, which contributes to aggressive nature of disease. Particularly, cells monocytic lineage, including monocytes, macrophages microglia, are affected. We investigated influence GBM-derived extracellular vesicles (EVs) on phenotype cells. Proteomic profiling showed GBM EVs be enriched with proteins functioning in matrix interaction leukocyte migration. appeared skew...
Genome editing of allogeneic T cells can provide "off-the-shelf" alternatives to autologous chimeric antigen receptor (CAR) cell therapies. Disruption α chain (TRAC) prevent graft-versus-host disease (GVHD) and removal CD52 (cluster differentiation 52) for a survival advantage in the presence alemtuzumab have previously been investigated using transcription activator-like effector nuclease (TALEN)-mediated knockout. Here, we deployed next-generation CRISPR-Cas9 linked CAR expression...
T cell maturation in Tcf-1(-/-) mice deteriorates progressively and halts completely around 6 mo of age. During fetal development thymocyte subpopulations seem normal, although total numbers are lower. By 4 to wk age, obvious blockades the differentiation CD4- 8- thymocytes observed at two distinct stages (CD44+ 25+ CD44- 25-), both which normally characterized by extensive proliferation. This lack expansion and/or was also when progenitor cells from aorta-gonad-mesonephros region (embryonic...
Previously, hepatic iron overload resembling that in hereditary hemachromatosis (HH) has been found beta 2-microglobulin knockout (beta 2m-/-) mice. We have now characterized metabolism 2m-/- The mutant mice fail to limit the transfer of from mucosal cells into plasma. Transferrin saturation is abnormally high. Pathologic depositions occur predominantly liver parenchymal cells. Reconstitution with normal hematopoietic redistributes Kupffer cells, but does not correct defect. conclude (a)...
Abstract Ewing sarcoma is an aggressive round cell with poor patient prognosis, particularly in cases of advanced‐stage disease. Dynamic tumor‐host immune interations within the tumor microenvironment may polarize situ responses and shape development and/or progression. To gain insight into nature tumour–host interactions microenvironment, presence spatial distribution infiltrating CD8 + /CD4 T‐lymphocytes were evaluated therapy‐naive sarcoma. Expression profiling 40 different chemokines...
Immunotherapy may be an excellent choice for treating osteosarcoma given its exceptionally high genomic instability, potentially generating neoantigens. In this study, we aim to investigate the HLA class I expression, PD-L1 and tumour-infiltrating lymphocytes in primary osteosarcomas relapses/metastases, as well their changes during disease progression. Tumour samples from multiple stages of (pretreatment biopsies, surgical resections osteosarcomas, relapses metastases) were collected...
An increase in the incidence of adenovirus (AdV) infection leading to death among children who have undergone allogeneic stem-cell transplantation has made it necessary find new ways monitor AdV infection. In this retrospective study, levels DNA serum samples obtained from 36 transplant recipients with stool cultures positive for were measured by polymerase chain reaction (PCR) semiquantitatively analyzing serial dilutions template. Six (86%) 7 died infection, compared only 2 (7%) 29 other...
Human adenovirus (HAdV) infections are increasingly frequent complications of allogeneic stem-cell transplantation (SCT), especially in children. Only a few data on the correlation between immune recovery and course HAdV infection available, HAdV-specific responses lacking.In prospective study, we determined DNA load plasma lymphocyte reconstitution 48 children after SCT. Additionally, humoral cellular were investigated.HAdV occurred 21 patients (44%), and, 6 these patients, progressed to...
Adenovirus (AdV) infections are an increasingly frequent and potentially fatal complication in allogeneic stem cell transplant recipients. To determine the antiviral potential of ribavirin unbiased way, 4 patients without immune recovery were prospectively analyzed by quantitative measurement plasma AdV DNA load. Administration at first signs dissemination was not accompanied a decrease load any these patients, increase even documented 3. These observations question to improve outcome for...
ABSTRACT Adenoviruses have been recognized as important pathogens in immunocompromised hosts. Particularly pediatric allogeneic stem cell transplant recipients, the morbidity of patients and mortality those with disseminated infections found to increase over last few years. Severe are predominantly but not exclusively caused by subgroup C adenoviruses. A multiplex real-time PCR assay using molecular beacons probes was developed enable monitoring adenovirus DNA simultaneous identification...
Abstract Purpose: Osteosarcoma and Ewing's sarcoma are the most common bone tumors in children adolescents. Despite intensive chemotherapy, patients with advanced disease have a poor prognosis, illustrating need for alternative therapies. Sarcoma cells susceptible to cytolytic activity of resting natural killer (NK) which can be improved by interleukin (IL)-15 stimulation. In this study, we explored whether function NK augmented specifically directed toward antibody-dependent cellular...
In osteosarcoma, the presence of tumor-infiltrating macrophages positively correlates with patient survival in contrast to negative effect tumor-associated patients other tumors. Liposome-encapsulated muramyl tripeptide (L-MTP-PE) has been introduced treatment osteosarcoma patients, which may enhance potential anti-tumor activity macrophages. Direct human against cells not described so far. Hence, we assessed cell growth after co-culture Monocyte-derived M1-like and M2-like were polarized...
High-grade osteosarcoma occurs predominantly in adolescents and young adults has an overall survival rate of about 60%, despite chemotherapy surgery. Therefore, novel treatment modalities are needed to prevent or treat recurrent disease. Natural killer (NK) cells lymphocytes with cytotoxic activity toward virus-infected malignant cells. We explored the feasibility autologous allogeneic NK cell–mediated therapies for chemotherapy-resistant chemotherapy-sensitive high-grade osteosarcoma. The...
Abstract Knowledge of human NK cells is based primarily on conventional CD56bright and CD56dim from blood. However, most cellular immune interactions occur in lymphoid organs. Based the coexpression CD69 CXCR6, we identified a third major cell subset tissues. This population represents 30–60% marrow, spleen, lymph node but absent CD69+CXCR6+ tissue have an intermediate expression CD56 high NKp46 ICAM-1. In contrast to circulating cells, they bimodal activating receptor DNAX accessory...
Anti-thymocyte globulin (ATG) is a lymphocyte depleting agent applied in hematopoietic stem cell transplantation (HSCT) to prevent rejection and Graft-versus-Host Disease (GvHD). In this study, we compared two rabbit ATG products, ATG-Genzyme (ATG-GENZ) ATG-Fresenius (ATG-FRES), with respect dosing, clearance of the active binding component, post-HSCT immune reconstitution clinical outcome. Fifty-eigth pediatric acute leukemia patients, (n=42 ATG-GENZ, n=16 ATG-FRES), who received...
Embryonic mice lacking functional Sox4 transcription factor die from cardiac failure at embryonic day (ED) 14. Heart morphogenesis in these embryos was analyzed hematoxylin-azophlochsin or immunohistochemically stained, 3-dimensionally reconstructed serial sections between ED12 and ED14. Although is expressed the endocardially derived tissue of both outflow tract atrioventricular canal, Sox4-deficient hearts only suffer defective transformation endocardial ridges into semilunar valves lack...
Abstract 1he mouse Sry ‐like transcription factor Sox‐4 is expressed in thymus, bone marrow, and gonads of adult mice. ‐deficient mice die at embryonic day E14 due to cardiac malformation. In transfer experiments irradiated recipients, B cell development was shown be severely impaired Sox‐4‐deficient progenitor cells. However, no drastic effects on T lymphocyte were noted, despite the high level expression gene thymus normal Here, we report a detailed analysis from progenitors. Explanted...
Epstein–Barr virus (EBV) persists lifelong in infected hosts despite the presence of antiviral immunity. Many viral antigens are expressed during lytic infection. Thus, for EBV to spread, it must have evolved effective ways evade immune recognition. Here, we report that HLA class II-restricted antigen presentation T helper cells is hampered lytic-phase protein gp42. This interference with cell activation involves association gp42 II peptide complexes. Using HLA-DR tetramers, identify a block...
Abstract Using the technique of homologous recombination in embryonic stem cells, a mouse strain without functional CD4 and CD8 genes has been generated. Surprisingly, these mice contain significant numbers αβ T cells. Although deficient for only do not show any cytotoxic response when their cells are stimulated with either alloantigen or viral antigen, − 8 generate alloreactive These bear cell receptor recognize major histocompatibility complex class I antigens. In addition fully allogeneic...