A5101787617- Monoclonal and Polyclonal Antibodies Research
- Hepatitis C virus research
- Cell Adhesion Molecules Research
- interferon and immune responses
- Cytokine Signaling Pathways and Interactions
- Liver Disease Diagnosis and Treatment
- Immunotherapy and Immune Responses
- Systemic Lupus Erythematosus Research
- T-cell and B-cell Immunology
- Neuroinflammation and Neurodegeneration Mechanisms
- HIV/AIDS drug development and treatment
- CAR-T cell therapy research
- Immune Response and Inflammation
- Immunodeficiency and Autoimmune Disorders
- Ethics in medical practice
- Hepatitis B Virus Studies
- Telemedicine and Telehealth Implementation
- Medical and Health Sciences Research
- Cell Image Analysis Techniques
- Inflammatory Bowel Disease
- Cutaneous Melanoma Detection and Management
- S100 Proteins and Annexins
- RNA Interference and Gene Delivery
- Viral Infections and Immunology Research
- Protein purification and stability
Sorrento Therapeutics (United States)
2019-2020
Beckman Research Institute
2019
City of Hope
2019
Friedrich Schiller University Jena
2015
RWTH Aachen University
2001
Despite the recognized role of tumor necrosis factor (TNF) in inflammation and neuronal degeneration, anti-TNF therapeutics failed to treat neurodegenerative diseases. Animal disease models had revealed antithetic effects two TNF receptors (TNFR) central nervous system, whereby TNFR1 has been associated with inflammatory degeneration TNFR2 neuroprotection. We here show therapeutic potential selective inhibition activation by ATROSAB, a TNFR1-selective antagonistic antibody, EHD2-scTNFR2, an...
Abstract Tumour necrosis factor (TNF) signalling is mediated via two receptors, TNF-receptor 1 (TNFR1) and 2 (TNFR2), which work antithetically to balance CNS immune responses involved in autoimmune diseases such as multiple sclerosis. To determine the therapeutic potential of selectively inhibiting TNFR1 mice with experimental encephalomyelitis, we used chimeric human/mouse knock-in allowing evaluation antagonistic anti-human antibody efficacy. Treatment after onset disease ATROSAB resulted...
Tumor necrosis factor (TNF) signals through two membrane receptors, TNFR1 and TNFR2, is known to be the major pathogenic mediator of chronic acute inflammatory diseases. Present clinical intervention based on neutralization ligand TNF. Selective inhibition TNF receptor 1 (TNFR1) provides an alternative opportunity neutralize pro-inflammatory activity while maintaining advantageous immunological responses mediated by including immune regulation, tissue homeostasis neuroprotection. We recently...
Therapeutics that block tumor necrosis factor (TNF), and thus activation of TNF receptor 1 (TNFR1) TNFR2, are clinically used to treat inflammatory diseases such as rheumatoid arthritis, bowel disease psoriasis. However, TNFR1 TNFR2 work antithetically balance immune responses involved in diseases. In particular, promotes inflammation tissue degeneration, whereas contributes modulation regeneration. We, therefore, have developed the monovalent antagonistic anti-TNFR1 antibody derivative...
Background Selective inhibition of TNFR1 signaling holds the potential to greatly reduce pro-inflammatory activity TNF, while leaving TNFR2 untouched, thus allowing for cell survival and tissue homeostasis. ATROSAB is a humanized antagonistic anti-TNFR1 antibody developed treatment inflammatory diseases. Methodology/Principal Findings The epitope resides in N-terminal region covering parts CRD1 CRD2. By site-directed mutagenesis, we identified Arg68 His69 as important residues binding....
Despite their well-recognized success in the clinic, antibodies generally do not penetrate cellular membranes to target intracellular molecules, many of which underlie incurable diseases. Here we show that covalently conjugating phosphorothioated DNA oligonucleotides enabled efficient internalization. Antibody cell penetration was partially mediated by membrane potential alteration. Moreover, without an antigen bind, levels modified underwent clearance, involved efflux and lysosomal...
Selective inhibition of tumor necrosis factor (TNF) signaling through the proinflammatory axis TNF-receptor 1 (TNFR1) while leaving pro-survival and regeneration-promoting signals via TNFR2 unaffected is a promising strategy to circumvent limitations complete TNF action by approved anti-TNF drugs. A previously developed humanized antagonistic TNFR1-specific antibody, ATROSAB, showed potent TNFR1-mediated cellular responses. Because parental mouse antibody H398 possesses even stronger...
The development of alternative therapeutic strategies to tumor necrosis factor (TNF)-blocking antibodies for the treatment inflammatory diseases has generated increasing interest. In particular, selective inhibition TNF receptor 1 (TNFR1) promises a more precise intervention, tackling only pro-inflammatory responses mediated by while leaving regenerative and pro-survival signals transduced TNFR2 untouched. We recently monovalent anti-TNFR1 antibody fragment (Fab 13.7) as an efficient...
Glycoprotein 130 (gp130) is a type I transmembrane protein and serves as the common signal-transducing receptor subunit of interleukin-6-type cytokines. Whereas membrane-distal half gp130 extracellular part confers ligand binding has been subject to intense investigation, structural functional features its membrane-proximal are poorly understood. On basis predictions tertiary structure, consists three fibronectin-type-III-like domains D4, D5 D6. Here we describe bacterial expression...
The humanized monoclonal antibody ATROSAB is targeting specifically the TNF receptor 1(TNFR1). a central mediator of inflammation and key target for intervention in inflammatory diseases such as rheumatoid arthritis, psoriasis Crohn’s Diseases. Notably, blockade second receptor, TNFR2, has been associated with increased sensitivity to viral infections or susceptibility demyelinating disorders lymphomas. In this context, selective inhibition TNF-induced TNFR1 but not TNFR2 signaling activity...
Glycoprotein 130 (gp130) is a type I transmembrane protein and serves as the common signal-transducing receptor subunit of interleukin-6-type cytokines. Whereas membrane-distal half gp130 extracellular part confers ligand binding has been subject to intense investigation, structural functional features its membrane-proximal are poorly understood. On basis predictions tertiary structure, consists three fibronectin-type-III-like domains D4, D5 D6. Here we describe bacterial expression...
Antibodies against the B cell-specific antigens CD20 and CD19 have markedly improved treatment of cell-derived lymphoma autoimmune diseases by depleting malignant autoreactive cells. However, since are also expressed on healthy cells, such antibodies lack disease specificity. Here, we optimize a previously developed concept that uses bispecific to induce apoptosis selectively in cells express death receptor CD95. We describe development characterization with CD95xCD20 CD95xCD19 specificity...
Abstract Vaccination efficacy is enhanced by targeting the antigen-presenting cell compartment. Here, we show that S1-Fc antigen delivery FcγR + compartment elicits anti-SARS-CoV-2 S1-antigen specific IgG production in vivo exerting biologically functional and protective activity against live virus infection, assessed a stringent experimental challenge assay vitro . The S1-domain of SARS-CoV-2 spike protein was genetically fused to human immunoglobulin Fc moiety, which contributes mediate...
Background: The achievement of EVR during triple therapy chronic HCV genotype 1 (G1) infection with BOC has been identified as predictor high SVR rates up to 90% well a shorten 24 weeks. present interim analysis the NOVUS observational study was aimed investigate in German real-life and identify baseline predictors EVR.
Background: Recently, renal impairment corresponding to insufficiency stage 3 has been reported in about 5% of patients treated for HCV genotype 1 infection with telaprevir or boceprevir (S Mauss et al., Hepatology 2014; 59:46 – 48). The present interim analysis the NOVUS observational study was conducted determine frequency 2 and insufficiencies elucidate associated risk factors mechanisms (pts) undergoing triple therapy German real-life.
TNF is involved in several degenerative brain diseases including stroke, Multiple Sclerosis, Parkinson's disease and Alzheimer's (AD). It became apparent recent years that TNFR1 TNFR2 signalling diverges with respect to its involvement neurodegeneration neuroprotection, respectively (Fontaine et al., 2002; Marchetti 2004; Dolga 2008; 2009; Fischer 2011; Naudé 2012; Maier 2013). Under chronic stimulation mediated counteracts pro‐apoptotic pathways by the activation of a PI3K, PKB/Akt...
Schwangerschaftsraten bei Leberzirrhose sind generell gering. Dennoch konnte in den letzten Jahren auf Grund verbesserter Therapieoptionen die Konzeptionsrate und der Anteil erfolgreicher Schwangerschaftsverläufe gesteigert werden.