A5039496067- Monoclonal and Polyclonal Antibodies Research
- HER2/EGFR in Cancer Research
- CAR-T cell therapy research
- Cell Adhesion Molecules Research
- Phagocytosis and Immune Regulation
- Glycosylation and Glycoproteins Research
- Cancer Immunotherapy and Biomarkers
- Microtubule and mitosis dynamics
- Chronic Lymphocytic Leukemia Research
- Endoplasmic Reticulum Stress and Disease
- Cancer Cells and Metastasis
- Asthma and respiratory diseases
- Lymphoma Diagnosis and Treatment
- Blood disorders and treatments
- Immune Response and Inflammation
- Acute Myeloid Leukemia Research
- Neutropenia and Cancer Infections
- Cancer Research and Treatments
- Multiple Myeloma Research and Treatments
- Chronic Myeloid Leukemia Treatments
- Neonatal and Maternal Infections
- Immune cells in cancer
- Bacterial Infections and Vaccines
- Bone health and treatments
- Cell death mechanisms and regulation
Seagen (United States)
2008-2023
Seagen (Canada)
2009
University of Washington
1993-2004
Celltechgen (United States)
2004
National Defense Medical Center
2002
Qingdao University
2002
Tri-Service General Hospital
2002
Seattle Children's Hospital
1996-1998
Children's Hospital & Medical Center
1996-1997
Harborview Medical Center
1997
Airway inflammation and remodeling in chronic asthma are characterized by airway eosinophilia, hyperplasia of goblet cells smooth muscle, subepithelial fibrosis. We examined the role leukotrienes a mouse model allergen-induced lung BALB/c mice, after intraperitoneal ovalbumin (OVA) sensitization on Days 0 14, received intranasal OVA periodically 14–75. The OVA-treated mice developed an extensive eosinophil mononuclear cell inflammatory response, hyperplasia, mucus occlusion airways. A...
Little is known about neutrophil (PMN) apoptosis in the acute respiratory distress syndrome (ARDS). We uses morphologic criteria to count apoptotic PMN bronchoalveolar lavage fluid (BAL) of 35 patients on Days 1, 3, 7, 14, and 21 ARDS 13 1 3 risk for ARDS. found that proportion BAL was low throughout course There no significant difference between percentage at with established or who lived (2.4%) died (1.8%). When normal human were incubated BAL, a significantly lower became (50 +/- 4%), as...
Antibody-drug conjugates (ADC) comprise targeting antibodies armed with potent small-molecule payloads. ADCs demonstrate specific cell killing in clinic, but the basis of their antitumor activity is not fully understood. In this study, we investigated degree to which payload release predicts ADC vitro and vivo were generated target different receptors on anaplastic large lymphoma line L-82, delivered same cytotoxic (monomethyl auristatin E, MMAE), found that intracellular concentration...
The goals of this study were to determine whether the Fas-dependent apoptosis pathway is active in lungs patients with acute respiratory distress syndrome (ARDS), and can contribute lung epithelial injury. We found that soluble Fas ligand (sFasL) present bronchoalveolar lavage (BAL) fluid before after onset ARDS. BAL concentration sFasL at ARDS was significantly higher who died. from induced distal cells, which express Fas, effect inhibited by blocking Fas/FasL system using three different...
The rat mast cell line RBL-2H3.1 contains an 85-kDa cytosolic phospholipase A2 (cPLA2) that is very likely involved in liberating arachidonate from membrane phospholipid for the synthesis of eicosanoids following stimulation with either calcium ionophore or IgE/antigen. In this study, intracellular location cPLA2 was determined using immunofluorescence microscopy and immuno-gold electron microscopy. nonstimulated cells, distributed throughout cytosol excluded nucleoplasm. Following...
Inhalation of antigen in immunized mice induces an infiltration eosinophils into the airways and increased bronchial hyperreactivity as are observed human asthma. We employed a model late-phase allergic pulmonary inflammation to address role leukotrienes (LT) mediating airway eosinophilia methacholine. Allergen intranasal challenge OVA-sensitized induced LTB4 LTC4 release airspace, widespread mucus occlusion airways, leukocytic tissue broncho-alveolar lavage fluid that was predominantly...
Group B streptococci (GBS) are the leading cause of meningitis in newborns. Although develops following bacteremia, precise mechanism or mechanisms whereby GBS leave bloodstream and gain access to central nervous system (CNS) not known. We hypothesized that produce because a unique capacity invade human brain microvascular endothelial cells (BMEC), single-cell layer which constitutes blood-brain barrier. In order test this hypothesis, we developed an vitro model with BMEC isolated from...
CD133/prominin-1 is a pentaspan transmembrane glycoprotein overexpressed in various solid tumours including colorectal and glioblastomas. CD133 was found here to be highly expressed >or=50% of pancreatic, gastric intrahepatic cholangiocarcinomas. Quantitative flow cytometric analysis showed that panel established hepatocellular, pancreatic cancer cell lines at levels higher than normal epithelial cells or bone marrow progenitor cells. A murine anti-human antibody (AC133) conjugated potent...
Treatment choices for acute myelogenous leukemia (AML) patients resistant to conventional chemotherapies are limited and novel therapeutic agents needed. IL3 receptor alpha (IL3Rα, or CD123) is expressed on the majority of AML blasts, there evidence that its expression increased leukemic relative normal hematopoietic stem cells, which makes it an attractive target antibody-based therapy. Here, we report generation preclinical characterization SGN-CD123A, antibody-drug conjugate using...
Immunized mice after inhalation of specific antigen have the following characteristic features human asthma: airway eosinophilia, mucus and Th2 cytokine release, hyperresponsiveness to methacholine. A model late-phase allergic pulmonary inflammation in ovalbumin-sensitized was used address role alpha4 integrin (CD49d) mediating hyperresponsiveness. Local, intrapulmonary blockade CD49d by intranasal administration mAb inhibited all signs lung inflammation, IL-4 IL-5 In contrast, on...
Pulmonary infections caused by Burkholderia (Pseudomonas) cepacia are an important cause of morbidity and mortality in cystic fibrosis (CF) patients. Several features suggestive cellular invasion intracellular sequestration B. CF persistence infection the face antibiotic therapy to which organism demonstrates vitro susceptibility a propensity bacteremic patients with CF. Epithelial cell was demonstrated A549 cells modified gentamicin protection assay. The kinetics appear be saturable....
SGN-40 is a therapeutic antibody targeting CD40, which induces potent anti-lymphoma activities via direct apoptotic signalling cells and by cell-mediated cytotoxicity. Here we show antibody-dependent cellular phagocytosis (ADCP) macrophages to contribute significantly the that antitumour effects of depend on Fc interactions.
The primary mechanism of antibody-drug conjugates (ADC) is targeted delivery a cytotoxic payload to tumor cells via cancer-associated membrane receptors. However, the microenvironment likely plays role in ADC penetration, distribution, and processing thus impacts overall antitumor activity. Here, we report on potential contribution Fc-FcγR interactions between ADCs tumor-associated macrophages (TAM) preclinical activities ADCs. In CD30+ L-428 Hodgkin lymphoma model, anti-CD30-vcMMAE...
ABSTRACT Group B streptococci (GBS) have been cultured from the chorioamnionic membrane of pregnant women, usually in association with chorioamnionitis and premature labor (K. A. Boggess, D. H. Watts, S. L. Hillier, M. Krohn, T. J. Benedetti, Eschenbach, Obstet. Gynecol. 87: 779–784, 1996). Colonization infection placental membranes can be a prelude to neonatal GBS infections even presence intact (R. Naeye E. C. Peters, Pediatrics 61: 171–177, 1978), suggesting that cause or establish...
Abstract Brentuximab vedotin, a CD30-directed antibody–drug conjugate (ADC), is approved for clinical use in multiple CD30-expressing lymphomas. The cytotoxic payload component of brentuximab vedotin monomethyl auristatin E (MMAE), highly potent microtubule-disrupting agent. Preclinical results provided here demonstrate that treatment cancer cells with or free MMAE leads to catastrophic disruption the microtubule network eliciting robust endoplasmic reticulum (ER) stress response culminates...
Despite therapeutic advances, the long-term survival rates for acute myeloid leukemia (AML) are estimated to be 10% or less, pointing need better treatment options. AML cells express marker CD33, making it amenable CD33-targeted therapy. Thus, in vitro and vivo anti-tumor activities of lintuzumab (SGN-33), a humanized monoclonal anti-CD33 antibody undergoing clinical evaluation, were investigated. In assays used assess ability mediate effector functions decrease production growth factors...
While antibody-drug conjugates (ADCs) are advancing through clinical testing and receiving new marketing approvals, improvements to the technology continue be developed in both academic industrial laboratories. Among key ADC attributes that can improved upon with their biodistribution pharmacokinetic properties. During course of development, it has become apparent conjugation drugs surface a monoclonal antibody alter its physicochemical characteristics manner results increased nonspecific...
Abstract Using a mouse mutagenesis screen, we have identified CD83 as being critical for the development of CD4+ T cells and their function postactivation. CD11c+ dendritic develop normally in mice with mutated gene but cell is substantially reduced. Additionally, now show that those mutant animal fail to respond following allogeneic stimulation. This at least part due an altered cytokine expression pattern characterized by increased production IL-4 IL-10 diminished IL-2 production. Thus,...
Lung expression of the extracellular matrix protein, laminin, and its receptor, laminin‐1 were examined in a mouse model asthma with airway remodelling. Ovalbumin (OVA) was administered to BALB/c mice, intraperitoneally on days 0 14, intranasally periodically between 14 75. The mice developed eosinophil mononuclear inflammatory cell infiltration fibrosis. On day 76, marked increase total laminin seen airways OVA‐treated compared controls by Western blot analysis. increased detected...
Integrin beta-6, a component of the heterodimeric adhesion receptor alpha-v/beta-6, is overexpressed in numerous solid tumors. Its expression has been shown by multiple investigators to be negative prognostic indicator diverse cancers including colorectal, non-small cell lung, gastric, and cervical. We developed SGN-B6A as an antibody-drug conjugate (ADC) directed integrin beta-6 deliver clinically validated payload monomethyl auristatin E (MMAE) cancer cells. The antibody specific for does...