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- W4362488440 abstract "<div>Abstract<p>Common lymphatic endothelial and vascular endothelial receptor-1 (Clever-1) is a multifunctional type-1 transmembrane protein that plays an important role in immunosuppression against tumors. Clever-1 is highly expressed in a subset of human tumor-associated macrophages and associated with poor survival. In mice, Clever-1 supports tumor growth and metastasis formation, and its deficiency or blockage induces T-cell–dependent killing of cancer cells. Therefore, targeting Clever-1 could lead to T-cell activation and restoration of immune response also in patients with cancer. This is studied in an on-going clinical trial [Macrophage Antibody To INhibit immune Suppression (MATINS); NCT03733990] in patients with advanced solid tumors where bexmarilimab, a humanized IgG4 antibody against human Clever-1, shows promising safety and efficacy.</p><p>Here, we report the humanization and nonclinical characterization of physicochemical properties, biological potency, and safety profile of bexmarilimab.</p><p>Bexmarilimab showed high affinity to Clever-1 on KG-1 cells and bound to Clever-1 on the surface of classical and intermediate monocytes derived from healthy human blood. Bexmarilimab inhibited the internalization of its natural ligand acetylated low-density lipoprotein into KG-1 cells and increased TNFα secretion from macrophages but did not impair phagocytic clearance. Bexmarilimab did not induce significant cytokine release in human whole-blood cultures, did not contain nonsafe immunogenic glycans, or show any significant binding to human Fcγ receptors or complement pathway component C1q. <i>In vivo</i>, bexmarilimab showed dose-dependent duration of monocyte Clever-1 receptor occupancy in cynomolgus monkeys but did not induce a cytokine storm up to a dose of 100 mg/kg.</p><p>In conclusion, these data support the clinical development of bexmarilimab for the restoration of immune response in cancers.</p></div>" @default.
- W4362488440 created "2023-04-05" @default.
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- W4362488440 date "2023-04-03" @default.
- W4362488440 modified "2023-10-14" @default.
- W4362488440 title "Data from Nonclinical Characterization of Bexmarilimab, a Clever-1–Targeting Antibody for Supporting Immune Defense Against Cancers" @default.
- W4362488440 doi "https://doi.org/10.1158/1535-7163.c.6543514.v1" @default.
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