A5070432137- Monoclonal and Polyclonal Antibodies Research
- Eosinophilic Esophagitis
- IL-33, ST2, and ILC Pathways
- Glycosylation and Glycoproteins Research
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Protein purification and stability
- Asthma and respiratory diseases
- Bacillus and Francisella bacterial research
- Protein Structure and Dynamics
- Galectins and Cancer Biology
- RNA and protein synthesis mechanisms
- Ubiquitin and proteasome pathways
- Parasitic Infections and Diagnostics
- Viral Infectious Diseases and Gene Expression in Insects
- RNA Interference and Gene Delivery
- Bacterial Identification and Susceptibility Testing
- Particle accelerators and beam dynamics
- Yersinia bacterium, plague, ectoparasites research
- Cancer Cells and Metastasis
- Multiple Sclerosis Research Studies
- Microtubule and mitosis dynamics
- Protein Degradation and Inhibitors
- Transgenic Plants and Applications
AstraZeneca (United Kingdom)
2020-2024
AstraZeneca (Brazil)
2024
AstraZeneca (Canada)
2020
Defence Science and Technology Laboratory
2004-2013
The University of Melbourne
2009
Los Alamos National Security (United States)
2000
University of New Mexico
1993-1994
Indiana University Bloomington
1993
Bristol Royal Infirmary
1989
Abstract In response to infections and irritants, the respiratory epithelium releases alarmin interleukin (IL)-33 elicit a rapid immune response. However, little is known about regulation of IL-33 following its release. Here we report that biological activity at receptor ST2 rapidly terminated in extracellular environment by formation two disulphide bridges, resulting an extensive conformational change disrupts binding site. Both reduced (active) bonded (inactive) forms can be detected lung...
Interleukin (IL)-33 is a broad-acting alarmin cytokine that can drive inflammatory responses following tissue damage or infection and promising target for treatment of disease. Here, we describe the identification tozorakimab (MEDI3506), potent, human anti-IL-33 monoclonal antibody, which inhibit reduced IL-33 (IL-33red) oxidized (IL-33ox) activities through distinct serum-stimulated 2 (ST2) receptor advanced glycation end products/epidermal growth factor (RAGE/EGFR complex) signalling...
Interleukin (IL)-13 is a pleiotropic T helper type 2 cytokine frequently associated with asthma and atopic dermatitis. IL-13-mediated signalling initiated by binding to IL-13Rα1, which then recruits IL-4Rα form heterodimeric receptor complex. IL-13 also binds IL-13Rα2, considered as either decoy or key mediator of fibrosis. IL-13-neutralising antibodies act preventing and/or IL-13Rα2. Tralokinumab (CAT-354) an human IgG4 monoclonal antibody that has shown clinical benefit in patients asthma....
Background Epithelial damage, repair and remodelling are critical features of chronic airway diseases including obstructive pulmonary disease (COPD). Interleukin (IL)-33 released from damaged epithelia causes inflammation via its receptor, serum stimulation-2 (ST2). Oxidation IL-33 to a non-ST2-binding form (IL-33 ox ) is thought limit activity. We investigated whether has functional activities that independent ST2 in the epithelium. Methods In vitro epithelial damage assays...
Three α-tubulin proteins contribute to microtubules during oogenesis and early embryogenesis in Drosophila melanogaster: αTUB84B, αTUB84D, αTUB67C. αTUB67C is unique two respects. It a structurally divergent α-tubulin, sharing only 67% amino acid identity with the generic isotypes αTUB84B its expression exclusively maternal. The genetic analysis of Tub67C gene described here demon strates that required for nuclear division oocyte embryo. Both meiosis cleavage-stage mitoses are severely...
The critical role played by IgE in allergic asthma is well-documented and clinically precedented, but some patients whom neutralization may still offer clinical benefit are excluded from treatment with the existing anti-IgE therapy, omalizumab, due to high total levels or body mass. In this study, we sought generate a novel affinity antibody (MEDI4212) potential treat broad severe patient population. Analysis of mass, allergen-specific cohort asthmatics was used support rationale for...
Glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) is part of a system signals involved in controlling T-cell activation. Targeting and agonizing GITR mice promotes antitumor immunity by enhancing the function effector T cells inhibiting regulatory cells. Here, we describe MEDI1873, novel hexameric human agonist comprising an IgG1 Fc domain, coronin 1A trimerization domain GITRL extracellular (ECD). MEDI1873 was optimized through systematic testing different...
Objective Immune complexes (ICs) play a critical role in the pathology of autoimmune diseases. The aim this study was to generate and characterise first-in-class anti-FcγRIIA antibody (Ab) VIB9600 (previously known as MEDI9600) that blocks IgG immune complex-mediated cellular activation for clinical development. Methods humanised optimised from IV.3 Ab. Binding affinity specificity were determined by Biacore ELISA. Confocal microscopy, Flow Cytometry-based assays binding competition used...
Chemical inducer of dimerization (CID) modules can be used effectively as molecular switches to control biological processes, and thus there is significant interest within the synthetic biology community in identifying novel CID systems. To date, have been primarily engineering cells for vitro applications. broaden their utility clinical setting, including potential cell gene therapies, identification should consider factors such safety pharmacokinetic profile small molecule inducer,...
Significance Insertion/deletion (InDel) mutations play key roles in genome and protein evolution. Despite their prominence evolutionary history, the potential of InDels for changing function engineering by directed evolution remains unexplored. Instead point mutagenesis is widely used. Here we create antibody libraries containing demonstrate that affinity maturation can be achieved this way, establishing an alternative to mutation strategies employed all previous vitro selections. These...
In vitro selection technologies are an important means of affinity maturing antibodies to generate the optimal therapeutic profile for a particular disease target. Here, we describe isolation parent antibody, KENB061 using phage display and solution phase selections with soluble biotinylated human IL-1R1. was matured targeted mutagenesis VH VL CDR3 NNS randomization. Affinity VHCDR3 VLCDR3 library blocks were recombined selected ribosome protocol. A direct comparison generated made determine...
Abstract Affinity- and stability-engineered variants of CTLA4-Ig fusion molecules with enhanced pharmacokinetic profiles could yield improved therapies the potential higher efficacy greater convenience to patients. In this study, our knowledge, we have, for first time, used in vitro evolution simultaneously optimize CTLA4 affinity stability. We selected binding both ligands, CD80 CD86, screened as dimeric Fc fusions directly functional assays identify stronger suppression T cell activation....
Heat shock proteins (Hsps) have attracted significant attention as protective antigens against a range of diseases caused by bacterial pathogens. However, more recently there been suggestions that the response is due to presence peptide components other than Hsps. We shown mice had immunized with purified heat protein 60 (Hsp60) isolated from Francisella tularensis were protected subsequent challenge some strains bacterium. this protection appeared be trace amounts lipopolysaccharide, which...
Computational free energy-based methods have the potential to significantly improve throughput and decrease costs of protein design efforts. Such must reach a high level reliability, accuracy, automation be effectively deployed in practical industrial settings way that impacts projects. Here, we present benchmark study for calculation relative changes protein-protein binding affinity single point mutations across variety systems from literature, using energy perturbation (FEP+) calculations....
<b>Background:</b> Interleukin (IL)-33 is a driver of inflammation and represents promising therapeutic target. IL-33 released in reduced form (IL-33red), which signals via ST2. Oxidation disulphide bond formation results IL-33ox, the newly discovered RAGE/EGFR complex. <b>Objective:</b> To develop dual-pharmacology anti-IL-33 monoclonal antibody (mAb). <b>Methods:</b> An oxidation resistant was used to isolate antibodies using phage display by screening for competition with soluble ST2...
Abstract Interleukin (IL)-33 is a broad-acting alarmin cytokine that can drive inflammatory responses following tissue damage or infection and promising target for treatment of disease. Here, we describe the identification tozorakimab (MEDI3506), potent, human anti-IL-33 monoclonal antibody, which inhibit reduced IL-33 (IL-33 red ) oxidized ox activities through distinct serum-stimulated 2 (ST2) receptor advanced glycation end products - epidermal growth factor (RAGE-EGFR complex) signalling...