- Monoclonal and Polyclonal Antibodies Research
- HER2/EGFR in Cancer Research
- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Head and Neck Cancer Studies
- Phagocytosis and Immune Regulation
- Chronic Lymphocytic Leukemia Research
- Cancer Diagnosis and Treatment
- Immunotherapy and Immune Responses
- Galectins and Cancer Biology
- Cell Adhesion Molecules Research
- Atherosclerosis and Cardiovascular Diseases
- T-cell and B-cell Immunology
- Lymphoma Diagnosis and Treatment
- Chemical Synthesis and Analysis
- Immune cells in cancer
- Radiopharmaceutical Chemistry and Applications
- Pancreatic and Hepatic Oncology Research
- Cutaneous lymphoproliferative disorders research
- Click Chemistry and Applications
- Immune Cell Function and Interaction
- Nanoparticle-Based Drug Delivery
- Salivary Gland Tumors Diagnosis and Treatment
- Hemophilia Treatment and Research
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
Genmab (Netherlands)
2004-2023
Genmab (United States)
2006-2023
The Netherlands Cancer Institute
2023
MorphoSys (Germany)
2023
Genmab (Denmark)
2013
University of Amsterdam
2000-2001
Amsterdam UMC Location University of Amsterdam
2000-2001
Tissue factor (TF) is aberrantly expressed in solid cancers and thought to contribute disease progression through its procoagulant activity capacity induce intracellular signaling complex with VIIa (FVIIa). To explore the possibility of using tissue as a target for an antibody-drug conjugate (ADC), panel human factor-specific antibodies (TF HuMab) was generated. Three HuMab, that induced efficient inhibition TF:FVIIa-dependent signaling, antibody-dependent cell-mediated cytotoxicity, rapid...
Advanced atherosclerotic lesions often contain adventitial lymphoid infiltrates, which occasionally nodular aggregates resembling follicles. The structural organization suggests that local maturation of B cells may take place at these sites, as described for the mucosa-associated tissue (MALT). This concept was evaluated by studying micro-anatomy and cellular composition infiltrates associated with advanced atherosclerosis aorta. Sections 22 aortas were stained immunohistochemically markers...
Abstract Epidermal growth factor receptor (EGF-R) overexpression is common in a large number of solid tumors and represents negative prognostic indicator. Overexpression EGF-R strongly tumor associated, this tyrosine kinase type considered an attractive target for Ab therapy. In study, we describe the evaluation mAb 2F8, high avidity human (IgG1κ) directed against EGF-R, developed using Ig transgenic mice. 2F8 effectively blocked binding EGF TGF-α to EGF-R. At saturating concentrations,...
The epidermal growth factor receptor (EGFR) is overexpressed on many solid tumors and represents an attractive target for antibody therapy. Here, we describe the effect of receptor-mediated internalization pharmacokinetics dose-effect relationship a therapeutic monoclonal (mAb) against EGFR (2F8). This mAb was previously found therapeutically active in mouse tumor models by two dose-dependent mechanisms action: blockade ligand binding induction antibody-dependent cell-mediated cytotoxicity....
Abstract Immunotherapy of cancer with CD3-targeting bispecific antibodies (CD3 bsAb) is a fast developing field, and multiple tumor-associated antigens (TAA) are evaluated for hematologic solid malignancies. The efficacy these CD3 bsAb usually examined in xenograft mouse tumor models human T cells or genetically engineered models, where TAA introduced. These often fail to fully recapitulate the natural environment, especially cancers, because interspecies differences. Here, we investigated...
Abstract Although immune checkpoint blockade (ICB) has shown remarkable clinical benefit in a subset of patients with melanoma and lung cancer, most experience no durable benefit. The receptor tyrosine kinase AXL is commonly implicated therapy resistance may serve as marker for therapy-refractory tumors, example melanoma, we previously demonstrated. Here, show that enapotamab vedotin (EnaV), an antibody–drug conjugate targeting AXL, effectively targets tumors display insensitivity to...
T-cell activation in atherosclerotic plaques is thought to be initiated by plaque-derived antigens, such as oxidized LDL (oxLDL). An alternative pathway of independent antigen stimulation, mediated the cytokine interleukin (IL)-15, was recently described. We investigated IL-15 expression relation plaque morphology, inflammatory cells, activation, and oxidation-specific epitopes use immunohistochemistry. In situ hybridization used evaluate mRNA expression. also studied proliferative response...
Abstract Background Elevated tissue factor (TF) expression, although restricted in normal tissue, has been reported multiple solid cancers, and expression associated with poor prognosis. This manuscript compares TF across various tumor types via immunohistochemistry a single study, which not performed previously. Aims To increase insight the prevalence cellular localization of cancer types, we detailed systematic analysis obtained from patients ovarian, esophageal, bladder, cervical,...
Epidermal growth factor receptor (EGFR) inhibitors are widely used in the treatment of cancer. EGFR-targeted is known to be associated with a high incidence dermatological adverse reactions, including papulopustular rash, which can dose-limiting and may affect compliance treatment. Currently, pathways involved EGFR inhibitor-induced rash poorly understood few options for this event available. Here, we developed model induction healthy human volunteers by subcutaneous injection anti-EGFR...
Immunohistochemistry is a widely accepted tool to investigate the presence and immunolocalization of cytokines in tissue sections at protein level. We have tested specificity reproducibility IFNgamma immunohistochemistry on with large panel anti-IFNgamma antibodies. Thirteen different commercially available antibodies, including seven advertised and/or regularly applied for immunohistochemistry/-cytochemistry, were using three-step streptavidin-biotin-peroxidase technique two-step...
Abstract Head and neck squamous cell carcinoma (HNSCC) is a solid tumor type that arises in the epithelial cells lining mucosal surfaces of upper aerodigestive tract. Long-term survival patients with advanced disease stage remains disappointing current treatment options. We show tissue factor abundantly expressed on patient-derived HNSCC lines, xenograft material, biopsies from HNSCC. Tisotumab vedotin (TV) an antibody–drug conjugate (ADC) directed to factor, protein many tumors. tumors were...
3066 Background: HuMax-Axl-ADC is an antibody-drug conjugate (ADC) that specifically targets Axl-expressing tumor cells. Aberrant expression of Axl, a receptor tyrosine kinase, has been described in solid and hematological malignancies, both primary tumors metastasis. Expression activation Axl associated with poor clinical prognosis cancers the lung, pancreas, esophagus breast. Moreover, implicated resistance to chemotherapy targeted therapy. Although mechanism behind cancer not fully...
Longitudinal imaging of intratumoral distributions antibodies in vivo mouse cancer models is great importance for developing therapies. In this study, multipinhole SPECT with sub–half-millimeter resolution was tested exploring radiolabeled directed toward the epidermal growth factor receptor (EGFr) and compared full 3-dimensional target expression assessed by immunohistochemistry. <b>Methods:</b><sup>111</sup>In-labeled zalutumumab, a human monoclonal EGFr-targeting antibody, administered at...
3066 Background: Tissue factor (TF) is the main initiator of coagulation, that starts when circulating VII(a) (FVII(a)) binds membrane bound TF. In addition, TF:FVIIa complex can initiate a pro-angiogenic signaling pathway by activation PAR-2. TF aberrantly expressed in many solid tumors, and expression has been associated with poor prognosis. TF-011-vcMMAE, an antibody-drug conjugate (ADC) under development for treatment composed human specific antibody (TF-011), proteaseEcleavable...
<p>Schematic scheme of in vivo experiments</p>
<p>Schematic scheme of in vivo experiments</p>
<p>Improved efficacy of chemotherapy when combined with tisotumab vedotin</p>
<div>Abstract<p>Head and neck squamous cell carcinoma (HNSCC) is a solid tumor type that arises in the epithelial cells lining mucosal surfaces of upper aerodigestive tract. Long-term survival patients with advanced disease stage remains disappointing current treatment options. We show tissue factor abundantly expressed on patient-derived HNSCC lines, xenograft material, biopsies from HNSCC. Tisotumab vedotin (TV) an antibody–drug conjugate (ADC) directed to factor, protein many...
<p>Tumor growth curves FaDu xenografts</p>
<p>Improved efficacy of chemotherapy when combined with tisotumab vedotin</p>
<div>Abstract<p>Head and neck squamous cell carcinoma (HNSCC) is a solid tumor type that arises in the epithelial cells lining mucosal surfaces of upper aerodigestive tract. Long-term survival patients with advanced disease stage remains disappointing current treatment options. We show tissue factor abundantly expressed on patient-derived HNSCC lines, xenograft material, biopsies from HNSCC. Tisotumab vedotin (TV) an antibody–drug conjugate (ADC) directed to factor, protein many...