A5021244456- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- vaccines and immunoinformatics approaches
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immune cells in cancer
- RNA Interference and Gene Delivery
- Prostate Cancer Treatment and Research
- Immune Response and Inflammation
- Genetic factors in colorectal cancer
- Genomics, phytochemicals, and oxidative stress
- Monoclonal and Polyclonal Antibodies Research
- Cutaneous Melanoma Detection and Management
- Cell Adhesion Molecules Research
- Cancer Cells and Metastasis
- Cancer Genomics and Diagnostics
- Multiple Sclerosis Research Studies
- Glutathione Transferases and Polymorphisms
- Tryptophan and brain disorders
- Ocular Oncology and Treatments
- Immunodeficiency and Autoimmune Disorders
- Multiple Myeloma Research and Treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Animal testing and alternatives
Radboud University Nijmegen
2015-2024
Radboud University Medical Center
2015-2024
Radboud Institute for Molecular Life Sciences
2014-2023
University Medical Center
2015-2023
Bipar
2016
de Duve Institute
2011-2013
UCLouvain
2013
Miltenyi Biotec (Germany)
2013
Instituto Tecnológico de Santo Domingo
2013
Leiden University Medical Center
2013
The blood-brain barrier (BBB) prevents the entrance of circulating molecules and immune cells into central nervous system. is formed by specialized brain endothelial that are interconnected tight junctions (TJ). A defective function BBB has been described for a variety neuroinflammatory diseases, indicating proper regulation essential maintaining homeostasis. Under pathological conditions, reactive oxygen species (ROS) significantly contribute to dysfunction inflammation in enhancing...
Vaccination against cancer by using dendritic cells has for more than a decade been based on generated ex vivo from monocytes or CD34(+) progenitors. Here, we report the first clinical study of therapeutic vaccination naturally occurring plasmacytoid (pDC). Fifteen patients with metastatic melanoma received intranodal injections pDCs activated and loaded tumor antigen-associated peptides vivo. In imaging showed that administered migrated distributed over multiple lymph nodes. Several mounted...
Tumor microenvironments feature immune inhibitory mechanisms that prevent T cells from generating effective antitumor responses. Therapeutic interventions aimed at disrupting these have been shown to enhance immunity, but they lack direct cytotoxic effects. Here, we investigated the effect of cancer chemotherapeutics on pathways. We observed exposure platinum-based markedly reduced expression cell molecule programmed death receptor-ligand 2 (PD-L2) both human DCs and tumor cells....
Thus far, dendritic cell (DC)-based immunotherapy of cancer was primarily based on in vitro-generated monocyte-derived DCs, which require extensive vitro manipulation. Here, we report a clinical study exploiting primary CD1c(+) myeloid naturally circulating the blood.Fourteen stage IV melanoma patients, without previous systemic treatment for metastatic disease, received autologous activated by only brief (16 hours) ex vivo culture and loaded with tumor-associated antigens tyrosinase...
Dendritic cell (DC)-based vaccination for cancer treatment has seen considerable development over recent decades. However, this field is currently in a state of flux toward niche-applications, owing to paradigm-shifts immuno-oncology mobilized by T cell-targeting immunotherapies. DC vaccines are typically generated using autologous (patient-derived) DCs exposed tumor-associated or -specific antigens (TAAs TSAs), the presence immunostimulatory molecules induce maturation, followed reinfusion...
Enhanced cerebrovascular permeability and cellular infiltration mark the onset of early multiple sclerosis lesions. So far, precise sequence these events their role in lesion formation disease progression remain unknown. Here we provide quantitative evidence that blood–brain barrier leakage is an event precedes massive development acute experimental allergic encephalomyelitis (EAE), animal correlate sclerosis. Cerebrovascular monocytes infiltrates were separately monitored by vivo MRI during...
It is unknown whether the route of administration influences dendritic cell (DC)-based immunotherapy. We compared effect intradermal versus intranodal a DC vaccine on induction immunologic responses in melanoma patients and examined concomitant interleukin (IL)-2 increases efficacy vaccine.HLA-A2.1(+) scheduled for regional lymph node dissection were vaccinated four times biweekly via or injection with 12 × 10⁶ to 17 mature DCs loaded tyrosinase gp100 peptides together keyhole limpet...
Abstract Reactive oxygen species (ROS) play an important role in various events underlying multiple sclerosis (MS) pathology. In the initial phase of lesion formation, ROS are known to mediate transendothelial migration monocytes and induce a dysfunction blood-brain barrier (BBB). this study, we describe beneficial effect antioxidant α-lipoic acid (LA) on these phenomena. vivo, LA dose-dependently prevented development clinical signs rat model for MS, acute experimental allergic...
Dendritic cells (DC) are professional antigen-presenting of the immune system that play a key role in regulating T cell-based immunity. In vivo, capacity DC to activate depends on their ability migrate cell areas lymph nodes as well maturation state. Depending cytokine-secreting profile, able skew response specific direction. particular, IL-12p70 producing drive towards helper 1 type response. A serious disadvantage current clinical grade ex vivo generated monocyte-derived is poor...
To evaluate the relevance of directing antigen-specific CD4(+) T helper cells as part effective anticancer immunotherapy, we investigated immunologic and clinical responses to vaccination with dendritic (DC) pulsed either MHC class I (MHC-I)-restricted epitopes alone or both II (MHC-I/II)-restricted epitopes. We enrolled 33 stage III IV HLA-A*02:01-positive patients melanoma in this study, whom 29 were evaluable for response. Patients received intranodal vaccinations cytokine-matured DCs...
Plasmacytoid dendritic cells (pDCs) play a crucial role in initiating immune responses by secreting large amounts of type I IFNs. Currently, the for human pDCs as professional APCs cross-presentation exogenous Ags is being re-evaluated. Human are equipped with broad repertoire Ag uptake receptors and an efficient Ag-processing machinery. In this study, we set out to investigate which receptor can best be deployed deliver (cross-)presentation. We show that targeting nanoparticles via C-type...
The tumor microenvironment is characterized by regulatory T cells, type II macrophages, myeloid-derived suppressor and other immunosuppressive cells that promote malignant progression. Here we report the identification of a novel BDCA1(+)CD14(+) population myeloid are expanded in melanoma patients present dendritic cell-based vaccines, where they suppress CD4(+) an antigen-specific manner. Mechanistic investigations showed expressed high levels immune checkpoint molecule PD-L1 to hinder...
<h3>Background</h3> Clinical benefit of cellular immunotherapy has been shown in patients with castration-resistant prostate cancer (CRPC)<b>.</b> We investigated the immunological response and clinical outcome vaccination blood-derived CD1c<sup>+</sup> myeloid dendritic cells (mDCs; cDC2) plasmacytoid DCs (pDCs). <h3>Methods</h3> In this randomized phase IIa trial<b>,</b> 21 chemo-naive CRPC received maximally 9 vaccinations mature mDCs, pDCs or a combination mDCs plus pDCs. were stimulated...
Tumor immunosurveillance plays a major role in melanoma, prompting the development of immunotherapy strategies. The gut microbiota composition, influencing peripheral and tumoral immune tonus, earned its credentials among predictors survival melanoma. MIND-DC phase III trial (NCT02993315) randomized (2:1 ratio) 148 patients with stage IIIB/C melanoma to adjuvant treatment autologous natural dendritic cell (nDC) or placebo (PL). Overall, 144 collected serum stool samples before after 2...
Electroporation of dendritic cells (DC) with mRNA encoding tumor-associated antigens (TAA) has multiple advantages compared to peptide loading. We investigated the immunologic and clinical responses vaccination mRNA-electroporated DC in stage III IV melanoma patients.Twenty-six HLA*02:01 patients scheduled for radical lymph node dissection (stage III) 19 irresectable locoregional or distant metastatic disease (referred as IV) were included. Monocyte-derived DC, electroporated gp100...