A5091455441- Radiopharmaceutical Chemistry and Applications
- Macrophage Migration Inhibitory Factor
- Nuclear Receptors and Signaling
- Monoclonal and Polyclonal Antibodies Research
- Carbon dioxide utilization in catalysis
- Synthesis and Characterization of Heterocyclic Compounds
- Peptidase Inhibition and Analysis
- Click Chemistry and Applications
- Microbial metabolism and enzyme function
- Synthesis of heterocyclic compounds
- Galectins and Cancer Biology
- ATP Synthase and ATPases Research
Abstract High levels of macrophage migration inhibitory factor (MIF) in patients with cancer are associated poor prognosis. Its redox-dependent conformational isoform, termed oxidized MIF (oxMIF), is a promising tumor target due to its selective occurrence lesions and at inflammatory sites. A first-generation anti-oxMIF mAb, imalumab, was investigated clinical trials advanced solid tumors, where it well tolerated showed signs efficacy. However, imalumab has short half-life humans, increased...
Macrophage Migration Inhibitory Factor (MIF) is a pleiotropic inflammatory cytokine that emerged as pivotal regulator in the pathogenesis of several autoimmune diseases including rheumatoid arthritis (RA). MIF occurs two immunologically distinct conformational isoforms, indicated reduced (redMIF) and oxidized (oxMIF) where latter exerts disease-related activities. In this study we demonstrate presence circulating oxMIF RA patients investigate vivo effects an oxMIF-neutralizing antibody...
Abstract Radioimmunotherapy (RIT) uses monoclonal antibodies to deliver radionuclides cancer cells or the tumor microenvironment and has shown promise in treating localized diffuse tumors. Although RIT agents have gained FDA/EMA approval for certain hematologic malignancies, effectiveness of solid tumors remains limited. In this study, we present PreTarg-it, a novel approach pretargeted RIT, providing optimized delivery payloads two-step regimen. The PreTarg-it is demonstrated by powerful...
MIF is a ubiquitous protein involved in proinflammatory processes, which undergoes an oxidation-driven conformational change to oxidized (ox)MIF. We demonstrate that hypochlorous acid, produced by neutrophil-released myeloperoxidase (MPO) under inflammatory conditions, effectively oxidizes into the oxMIF isoform, specifically recognized anti-oxMIF therapeutic antibody, ON104. NMR investigation of MPO system revealed increased flexibility throughout structure, including at several catalytic...
<div>Abstract<p>Radioimmunotherapy (RIT) uses monoclonal antibodies to deliver radionuclides cancer cells or the tumor microenvironment and has shown promise in treating localized diffuse tumors. Although RIT agents have gained FDA/EMA approval for certain hematologic malignancies, effectiveness of solid tumors remains limited. In this study, we present PreTarg-it, a novel approach pretargeted RIT, providing optimized delivery payloads two-step regimen. The PreTarg-it is...
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<div>Abstract<p>Radioimmunotherapy (RIT) uses monoclonal antibodies to deliver radionuclides cancer cells or the tumor microenvironment and has shown promise in treating localized diffuse tumors. Although RIT agents have gained FDA/EMA approval for certain hematologic malignancies, effectiveness of solid tumors remains limited. In this study, we present PreTarg-it, a novel approach pretargeted RIT, providing optimized delivery payloads two-step regimen. The PreTarg-it is...
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Background: Rigorous assessment of antibody developability is crucial for optimizing lead candidates before progressing to clinical studies. Recent advances in predictive tools protein structures, surface properties, stability, and immunogenicity have streamlined the development new biologics. However, accurate prediction impact single amino acid substitutions on structures remains challenging, due diversity complementarity-determining regions (CDRs), particularly CDR3s. Methods: In this...
Abstract Background: Macrophage Migration Inhibitory Factor (MIF) has been described as a pleiotropic cytokine known to exacerbate tumor growth (Chesney and Mitchell, 2015). Due its ubiquitous nature, MIF can be considered an inappropriate target for therapeutic intervention. However, we discovered oxidized (oxMIF) the disease-related isoform of MIF, which is specifically present in tissue (Schinagl A et al., 2016). 1st generation anti-oxMIF monoclonal antibody (mAb) demonstrated acceptable...
<div>Abstract<p>High levels of macrophage migration inhibitory factor (MIF) in patients with cancer are associated poor prognosis. Its redox-dependent conformational isoform, termed oxidized MIF (oxMIF), is a promising tumor target due to its selective occurrence lesions and at inflammatory sites. A first-generation anti-oxMIF mAb, imalumab, was investigated clinical trials advanced solid tumors, where it well tolerated showed signs efficacy. However, imalumab has short half-life...
<div>Abstract<p>High levels of macrophage migration inhibitory factor (MIF) in patients with cancer are associated poor prognosis. Its redox-dependent conformational isoform, termed oxidized MIF (oxMIF), is a promising tumor target due to its selective occurrence lesions and at inflammatory sites. A first-generation anti-oxMIF mAb, imalumab, was investigated clinical trials advanced solid tumors, where it well tolerated showed signs efficacy. However, imalumab has short half-life...