A5070474353- Peptidase Inhibition and Analysis
- Cell Adhesion Molecules Research
- Monoclonal and Polyclonal Antibodies Research
- HER2/EGFR in Cancer Research
- Complement system in diseases
- Occupational and environmental lung diseases
- Cancer Research and Treatments
- Signaling Pathways in Disease
- Platelet Disorders and Treatments
- Cancer, Hypoxia, and Metabolism
- Superconducting Materials and Applications
- Pancreatic function and diabetes
- Birth, Development, and Health
- Cellular Mechanics and Interactions
- Nanoparticle-Based Drug Delivery
- Protease and Inhibitor Mechanisms
- Liver physiology and pathology
- Fibroblast Growth Factor Research
- Advanced Biosensing Techniques and Applications
- Immune cells in cancer
- Magnetic properties of thin films
- Magnetic Properties and Applications
- Wound Healing and Treatments
- Pregnancy and preeclampsia studies
- Pregnancy and Medication Impact
Rigshospitalet
2019-2025
University of Copenhagen
2015-2025
Technical University of Denmark
2023
National Institute of Dental and Craniofacial Research
2019
National Institutes of Health
2019
Antibody-drug conjugates (ADCs) hold promise to advance targeted therapy of pancreatic ductal adenocarcinoma (PDAC), where the desmoplastic tumor stroma challenges effective treatment. Here, we explored urokinase plasminogen activator receptor (uPAR) as a candidate ADC target in PDAC, harnessing its massive tumoral and stromal expression this stroma-dense tumor. We generated site-specific offering high-affinity, cross-species reactivity, efficient internalization anti-uPAR monoclonal...
A human epidermal growth factor receptor 2 (HER2)-specific nanobody called 2Rs15d, containing a His3LysHis6 segment at the C-terminus, was recombinantly produced. Subsequent site-selective acylation on C-terminally activated lysine residue allowed installation of cytotoxin monomethyl auristatin E-functionalized cathepsin B-sensitive payload to provide highly homogenous nanobody–drug conjugate (NBC), which demonstrated high potency and selectivity for HER2-positive breast cancer models.
Macrophage plasticity, cellular origin, and phenotypic heterogeneity are perpetual challenges for studies addressing the biology of this pivotal immune cell in development, homeostasis, tissue remodeling/repair. Consequently, a myriad macrophage subtypes has been described these contexts. To facilitate identification functional vivo, here we used flow cytometry-based assay that allows detailed phenotyping macrophages engaged extracellular matrix (ECM) degradation. Of five identified...
It has recently been shown that hepatocyte growth factor activator inhibitor-2 (HAI-2) is able to suppress carcinogenesis induced by overexpression of matriptase, as well cause regression individual established tumors in a mouse model system. However, the role HAI-2 poorly understood. In this study, we describe 3 mutations binding loop Kunitz domain 1 (K42N, C47F and R48L) delay SEA cleavage leading accumulation non-SEA cleaved matriptase endoplasmic reticulum (ER). We suggest that, like...
Abstract The membrane-anchored matrix metalloprotease MT1-MMP is a potent collagenolytic enzyme with well-established role in extracellular turnover and cellular invasion into collagen-rich tissues. highly expressed various types of cancer has been demonstrated to be directly involved several stages tumor progression, including primary growth, angiogenesis, metastasis. Osteosarcoma the most common type bone cancer. This disease characterized by invasive leading extensive destruction,...
We herein describe the cell-specific release of alcohol-containing payloads via a sulfatase-sensitive linker in antibody-drug conjugates (ADCs). The shows efficient sulfatase-mediated and high stability human mouse plasma. In vitro evaluation demonstrates potent antigen dependent toxicity towards breast cancer cell lines.
C-type lectins that contain collagen-like domains are known as collectins. These proteins present both in the circulation and extravascular compartments central players of innate immune system, contributing to first-line defenses against viral, bacterial, fungal pathogens. The collectins mannose-binding lectin (MBL) surfactant protein D (SP-D) regulated by tissue fibroblasts at sites via an endocytic mechanism governed urokinase plasminogen activator receptor-associated (uPARAP or Endo180),...
Malignant mesothelioma (MM) is a highly aggressive cancer with limited therapeutic options. We have previously shown that the endocytic collagen receptor, uPARAP, upregulated in certain cancers and can be therapeutically targeted. Public RNA expression data display uPARAP overexpression MM. Thus, to evaluate its potential use diagnostics therapy, we quantified by immunohistochemical H-score formalin-fixed paraffin-embedded bioptic/surgical human tissue samples microarrays. detected...
Preeclampsia is characterized by disturbed placentation, hypertension, proteinuria, and suppression of plasma renin, angiotensin II, aldosterone. Regulated activity tissue serine proteases, prostasin, matriptase necessary for normal placental development in mice. Prostasin activates the renal epithelial sodium channel. We hypothesized that preeclampsia associated with low prostasin expression placenta spillover into urine across defect glomerular barrier.In a cross-sectional study, 20...
Objective: The serine protease prostasin (PRSS8, CAP1) and its activator matriptase inhibitor nexin-1 are necessary for normal placental development in mice. Prostasin is regulated by aldosterone the kidney may activate epithelial sodium channel (ENaC). Preeclampsia characterized disturbed placentation, suppression of avid renal retention with hypertension. It was hypothesized that preeclampsia associated low expression placenta spillover into urine across defect glomeular barrier. Design...