A5081340725- Monoclonal and Polyclonal Antibodies Research
- HER2/EGFR in Cancer Research
- Glycosylation and Glycoproteins Research
- Cell Adhesion Molecules Research
- Chronic Lymphocytic Leukemia Research
- Calcium signaling and nucleotide metabolism
- Advanced Biosensing Techniques and Applications
- Radiopharmaceutical Chemistry and Applications
- Nanofabrication and Lithography Techniques
- Multiple Myeloma Research and Treatments
- CAR-T cell therapy research
- Toxin Mechanisms and Immunotoxins
- Click Chemistry and Applications
- Protein purification and stability
- Platelet Disorders and Treatments
- Advanced Breast Cancer Therapies
- Blood Coagulation and Thrombosis Mechanisms
- Pharmacogenetics and Drug Metabolism
- Analytical Methods in Pharmaceuticals
- Phagocytosis and Immune Regulation
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Cancer-related Molecular Pathways
- Transgenic Plants and Applications
- Cell death mechanisms and regulation
- Hemophilia Treatment and Research
Genmab (Netherlands)
2013-2023
Genmab (United States)
2011-2014
Genmab (Denmark)
2013
Amsterdam UMC Location University of Amsterdam
2005-2006
Marinus Pharmaceuticals (United States)
2006
The promise of bispecific antibodies (bsAbs) to yield more effective therapeutics is well recognized; however, the generation bsAbs in a practical and cost-effective manner has been formidable challenge. Here we present technology for efficient with normal IgG structures that amenable both antibody drug discovery development. process involves separate expression two parental antibodies, each containing single matched point mutations CH3 domains. are mixed subjected controlled reducing...
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...
Antibody-drug conjugates (ADC) are designed to be stable in circulation and release potent cytotoxic drugs intracellularly following antigen-specific binding, uptake, degradation tumor cells. Efficient internalization routing lysosomes where proteolysis can take place is therefore essential. For many cell surface proteins carbohydrate structures on cells, however, the magnitude of these processes insufficient allow for an effective ADC approach. We hypothesized that we could overcome this...
Abstract Antibody–drug conjugates (ADC) are emerging as powerful cancer treatments that combine antibody-mediated tumor targeting with the potent cytotoxic activity of toxins. We recently reported development a novel ADC delivers payload monomethyl auristatin E (MMAE) to cells expressing tissue factor (TF). By carefully selecting TF-specific antibody interferes TF:FVIIa-dependent intracellular signaling, but not procoagulant TF, an was developed (TF-011-MMAE/HuMax-TF-ADC) efficiently kills...
HexaBody®-CD38 (GEN3014) is a hexamerization-enhanced human IgG1 that binds CD38 with high affinity. The E430G mutation in its Fc domain facilitates the natural process of antibody hexamer formation upon binding to cell surface, resulting increased C1q and potentiated complement-dependent cytotoxicity (CDC).Co-crystallization studies were performed identify interface HexaBody-CD38 CD38. HexaBody-CD38-induced CDC, antibody-dependent cellular (ADCC), phagocytosis (ADCP), trogocytosis,...
Objectives: We developed a physiologically based pharmacokinetic pharmacodynamic (PBPK-PD) model to simulate direct and bystander cytotoxic effects of antibody drug conjugates (ADCs) in the tumor microenvironment (TME) assess their toxicological profiles various tissues. Local sensitivity analysis (LSA) global (GSA) explored how parameters impact ADC efficacy toxicity, with focus on GSA's effectiveness identifying non-monotonous parameter influences.Methods: created an PBPK-PD by integrating...
The human epidermal growth factor receptor (HER)2 provides an excellent target for selective delivery of cytotoxic drugs to tumor cells by antibody-drug conjugates (ADC) as has been clinically validated ado-trastuzumab emtansine (KadcylaTM). While selecting a suitable antibody ADC approach often takes specificity and efficient antibody-target complex internalization into account, the characteristics optimal candidate remain poorly understood. We studied large panel HER2 antibodies identify...
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>PDF file - 27K, Antibody cross-competition studies; Alphascreen Assay to detect ERK phosphorylation.</p>
<div>Abstract<p>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...
<div>Abstract<p>Antibody–drug conjugates (ADC) are designed to be stable in circulation and release potent cytotoxic drugs intracellularly following antigen-specific binding, uptake, degradation tumor cells. Efficient internalization routing lysosomes where proteolysis can take place is therefore essential. For many cell surface proteins carbohydrate structures on cells, however, the magnitude of these processes insufficient allow for an effective ADC approach. We hypothesized...
<p>PDF file - 27K, Antibody cross-competition studies; Alphascreen Assay to detect ERK phosphorylation.</p>
<div>Abstract<p>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...
<div>Abstract<p>Antibody–drug conjugates (ADC) are designed to be stable in circulation and release potent cytotoxic drugs intracellularly following antigen-specific binding, uptake, degradation tumor cells. Efficient internalization routing lysosomes where proteolysis can take place is therefore essential. For many cell surface proteins carbohydrate structures on cells, however, the magnitude of these processes insufficient allow for an effective ADC approach. We hypothesized...
<p>Supplementary Figure legends for figures S1, S2 and S3</p>
<p>Lysosomal transport of a bispecific antibody targeting integrin-β1 and CD63</p>
<p>Binding of bsHER2xCD63his to SK-OV-3 cells</p>
<p>Schematic overview of the mechanism action bsHER2xCD63his-ADC</p>
<p>Lysosomal transport of a bispecific antibody targeting integrin-β1 and CD63</p>