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A recombinant human IgG1 Fc multimer designed to mimic the active fraction of IVIG in autoimmunity.

JCI insight (2019-01-25)
Xiaoyu Zhang, Jane Owens, Henrik S Olsen, Edward So, Erin Burch, Mark C McCroskey, Xianfeng Li, Gregory L Weber, Donald Bennett, Denis Rybin, Hua Zhou, Haiping Hao, Emmanuel Y Mérigeon, David S Block, Gregory LaRosa, Scott E Strome
ABSTRACT

The antiinflammatory effects of i.v. Ig (IVIG) in the treatment of autoimmune disease are due, in part, to the Fc fragments of Ig aggregates. In order to capitalize on the known antiinflammatory and tolerogenic properties of Ig Fc aggregates, we created a recombinant human IgG1 Fc multimer, GL-2045. In vitro, GL-2045 demonstrated high-avidity binding to Fc receptors, blocked the binding of circulating immune complexes from patients with rheumatoid arthritis to human Fcγ receptors (FcγRs), and inhibited antibody-mediated phagocytosis at log order-lower concentrations than IVIG. In vivo, administration of GL-2045 conferred partial protection against antibody-mediated platelet loss in a murine immune thrombocytopenic purpura (ITP) model. GL-2045 also suppressed disease activity in a therapeutic model of murine collagen-induced arthritis (CIA), which was associated with reduced circulating levels of IL-6. Furthermore, GL-2045 administration to nonhuman primates (NHPs) transiently increased systemic levels of the antiinflammatory cytokines IL-10 and IL-1RA, reduced the proinflammatory cytokine IL-8, and decreased surface expression of CD14 and HLA-DR on monocytes. These findings demonstrate the immunomodulatory properties of GL-2045 and suggest that it has potential as a treatment for autoimmune and inflammatory diseases, as a recombinant alternative to IVIG.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Human IgG (Fab specific)−FITC antibody produced in goat, affinity isolated antibody, buffered aqueous solution
Millipore
MILLIPLEX® Non-Human Primate Cytokine Magnetic Bead Panel - Immunology Multiplex Assay, Simultaneously analyze multiple cytokine and chemokine biomarkers with Bead-Based Multiplex Assays using the Luminex technology, in mouse serum, plasma and cell culture samples.

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