ON104, a novel antibody targeting oxidized Macrophage Migration Inhibitory Factor (oxMIF) shows efficacy in preclinical models of chronic inflammation
نویسندگان
چکیده
Abstract Macrophage Migration Inhibitory Factor (MIF) is a pleiotropic inflammatory cytokine, ubiquitously present in various tissues and the circulation of healthy subjects. MIF primary counter-actor glucocorticoids that emerged as pivotal regulator chronic inflammation. During inflammation, converts into oxidized (ox)MIF which was described pathogenic druggable isoform MIF. ON104, fully human antibody, engineered to specifically neutralize oxMIF without triggering immune cell effector functions. ON104 tested three experimental models diseases (CIDs): Glomerulonephritis (GN) WKY rats, Collagen-Induced Arthritis (CIA) DBA/1j mice; adoptive T-cell transfer colitis SCID mice. At disease onset, administered at different dose levels twice week for 1, 3, 8 weeks GN, CIA, colitis, respectively. Clinical evaluations, blood tissue sampling were done all individual animals. In GN model, significantly reduced proteinuria, hematuria, CD68 +macrophage infiltration within inflamed kidneys. ameliorated severity arthritis indicated by paw thickness, decreased score. Furthermore, treatment with substantially attenuated clinical signs preventing body weight loss restoring stool consistency compared vehicle-treated controls. Our findings substantiate role pathogenesis CIDs. Thus, has potential become well-tolerated therapeutic antibody treating patients
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ژورنال
عنوان ژورنال: Journal of Immunology
سال: 2023
ISSN: ['1550-6606', '0022-1767']
DOI: https://doi.org/10.4049/jimmunol.210.supp.85.02