A5082357720- Immune cells in cancer
- Monoclonal and Polyclonal Antibodies Research
- Chemokine receptors and signaling
- Alzheimer's disease research and treatments
- Nanoplatforms for cancer theranostics
- Biochemical and Structural Characterization
- Immunotherapy and Immune Responses
- Down syndrome and intellectual disability research
- Chemical Synthesis and Analysis
- Histone Deacetylase Inhibitors Research
- Epigenetics and DNA Methylation
- Advanced Electron Microscopy Techniques and Applications
- T-cell and B-cell Immunology
- RNA Interference and Gene Delivery
- Cannabis and Cannabinoid Research
- Cell Adhesion Molecules Research
- S100 Proteins and Annexins
- Advanced biosensing and bioanalysis techniques
- Advanced Glycation End Products research
- Force Microscopy Techniques and Applications
- Fibroblast Growth Factor Research
- Peptidase Inhibition and Analysis
- Protease and Inhibitor Mechanisms
- Pancreatic function and diabetes
- Phagocytosis and Immune Regulation
Radboud University Nijmegen
2018-2025
Radboud University Medical Center
2018-2025
Radboud Institute for Molecular Life Sciences
2018-2023
University Medical Center
2023
Leiden University
2016
Increased levels of tumor-associated macrophages (TAMs) are indicators poor prognosis in most cancers. Although antibodies and small molecules blocking the recruitment to tumors under evaluation as anticancer therapies, these strategies not specific for macrophage subpopulations. Herein we report first enzyme-activatable chemokine conjugates effective targeting defined subsets live tumors. Our constructs exploit high expression receptors (e.g., CCR2) activity cysteine cathepsins TAMs target...
Antibody conjugates are the foundation of a wide range diagnostic and therapeutic applications. Although many antibody-conjugation techniques robust efficient, obtaining homogeneous multimeric conjugation products remains challenging. Here we report modular versatile technique for site-directed multivalent antibodies via small-protein ubiquitin. Specifically, multiple ubiquitin fusions with antibodies, antibody fragments, nanobodies, peptides or small molecules such as fluorescent dyes can...
Triazole ureas constitute a versatile class of irreversible inhibitors that target serine hydrolases in both cells and animal models. We have previously reported triazole can act as selective CNS-active for diacylglycerol lipases (DAGLs), enzymes responsible the biosynthesis 2-arachidonoylglycerol (2-AG) activates cannabinoid CB1 receptor. Here, we report enantio- diastereoselective synthesis structure–activity relationship studies. found 2,4-substituted with biphenylmethanol group provided...
Cathepsin B is a cysteine protease that implicated in multiple aspects of Alzheimer's disease pathogenesis. The endogenous inhibitor this enzyme, cystatin (CSTB) encoded on chromosome 21. Thus, individuals who have Down syndrome, genetic condition caused by having an additional copy 21, extra the enzyme. Individuals syndrome are also at significantly increased risk developing early-onset (EOAD). impact CSTB development people not well understood. Here we compared biology cathepsin and had...
Functionalized antibodies and antibody fragments have found applications in the fields of biomedical imaging, theranostics, antibody–drug conjugates (ADC). In addition, therapeutic theranostic approaches benefit from possibility to deliver more than one type cargo target cells, further challenging stochastic labeling strategies. Thus, bioconjugation methods reproducibly obtain defined homogeneous bearing multiple different molecules, without compromising affinity, are demand. Here, we...
Cathepsin S is a lysosomal cysteine protease highly expressed in immune cells such as dendritic cells, B and macrophages. Its functions include extracellular matrix breakdown cleavage of cell adhesion molecules to facilitate motility, well the invariant chain during maturation major histocompatibility complex II. The identification these diverse specific has brought challenge delineating cathepsin activity with great spatial precision, relative related enzymes substrates. Here, development...
Abstract Despite new treatments, cancer remains the second leading cause of death worldwide with breast being most common type. Of these deaths, majority are due to formation distant metastases. While immunotherapies have shown some success in primary tumors, their efficacy combating metastases has been lacking. Thus we aim investigate hypothesis that immune responses at metastatic site contribute limitations current therapies.Within last decade, microscopy technologies now enable real-time...
Abstract Cathepsin B is a cysteine protease that implicated in multiple aspects of Alzheimer’s disease pathogenesis. The endogenous inhibitor this enzyme, cystatin ( CSTB) encoded on chromosome 21. Thus, individuals who have Down syndrome, genetic condition caused by having an additional copy 21, extra the enzyme. Individuals syndrome are also at significantly increased risk developing early-onset (EOAD). impact development people not well understood. Here we compared biology cathepsin and...
Many autoimmune diseases are characterized by B cells that mistakenly recognize autoantigens and produce antibodies toward self-proteins. Current therapies aim to suppress the immune system, which is associated with adverse effects. An attractive more specific approach target autoreactive selectively through their unique B-cell receptor (BCR) using an autoantigen coupled effector molecule able modulate activity. The cellular response upon antigen binding, such as internalization, impacts...
Increased levels of tumor-associated macrophages (TAMs) are indicators poor prognosis in most cancers. Although antibodies and small molecules blocking the recruitment to tumors under evaluation as anticancer therapies, these strategies not specific for macrophage subpopulations. Herein we report first enzyme-activatable chemokine conjugates effective targeting defined subsets live tumors. Our constructs exploit high expression receptors (e.g., CCR2) activity cysteine cathepsins TAMs target...
Tumour-associated macrophages (TAMs) support tumour development and have emerged as important regulators of therapeutic response to cytostatic agents. To target TAMs, we developed a novel drug delivery approach which induces release it inhibits cysteine cathepsin activity. This inhibitory prodrug (IPD) establishes self-regulated system where stops after all cathepsins are inhibited. could improve the window for drugs with severe side effects. We demonstrate characterise this self-regulation...
Abstract Background People with Down syndrome (DS) have a high genetic risk of developing Alzheimer’s disease (AD) ‐related dementia and pathology. Triplication human chromosome 21 (Hsa21)‐located gene APP play an important role in AD Wiseman et al. demonstrated that triplication or genes on Hsa21, other than exacerbates amyloid‐β pathology transgenic mouse model. Multiple lines evidence indicate cysteine cathepsin activity influences cleavage Aβ accumulation. Cystine cathepsins are...
I. Abstract Functionalized antibodies and antibody fragments have found applications in the fields of biomedical imaging, theragnostics, antibody-drug conjugates (ADC). Antibody functionalization is classically achieved by coupling payloads onto lysine or cysteine residues. However, such stochastic strategies typically lead to heterogenous products, bearing a varying number payloads. This affects bioconjugate efficacy stability, as well its vivo biodistribution, therapeutic index, while...
Tumor associated macrophages (TAMs) support tumor development and have emerged as important regulators of therapeutic response to cytostatic agents. To target TAMs, we developed a novel drug delivery approach which induces release in inhibition pro-tumor cysteine cathepsin activity. Such inhibitory prodrug (IPD) establishes self-regulated system where stops after all cathepsins are inhibited. This could improve the window for drugs with severe side effects. We demonstrate this...