Production of recombinant human IgG1 Fc with beneficial N-glycosylation pattern for anti-inflammatory activity using genome-edited chickens.

Abstract

Intravenous immunoglobulin (IVIG) is a plasma-derived polyclonal IgG used for treatment of autoimmune diseases. Studies show that α-2,6 sialylation of the Fc improves anti-inflammatory activity. Also, afucosylation of the Fc efficiently blocks FcγRIIIA by increasing monovalent affinity to this receptor, which can be beneficial for treatment of refractory immune thrombocytopenia (ITP). Here, we generated genome-edited chickens that synthesize human IgG1 Fc in the liver and secrete α-2,6 sialylated and low-fucosylated human IgG1 Fc (rhIgG1 Fc) into serum and egg yolk. Also, rhIgG1 Fc has higher affinity for FcγRIIIA than commercial IVIG. Thus, rhIgG1 Fc efficiently inhibits immune complex-mediated FcγRIIIA crosslinking and subsequent ADCC response. Furthermore, rhIgG1 Fc exerts anti-inflammatory activity in a passive ITP model, demonstrating chicken liver derived rhIgG1 Fc successfully recapitulated efficacy of IVIG. These results show that genome-edited chickens can be used as a production platform for rhIgG1 Fc with beneficial N-glycosylation pattern for anti-inflammatory activities.

• Authors: Jin Se Park, Hee Jung Choi, Kyung Min Jung, Kyung Youn Lee, Ji Hyeon Shim, Kyung Je Park, Young Min Kim, Jae Yong Han
• Journal: Communications biology (Commun Biol) Vol. 6 Issue 1 Pg. 589 (06 01 2023) ISSN: 2399-3642 [Electronic] England
• PMID: 37264071 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2023. The Author(s).

Chemical References

• Immunoglobulin G
• Immunoglobulins, Intravenous
• Anti-Inflammatory Agents

Topics

• Humans
• Animals
• Immunoglobulin G
• Immunoglobulins, Intravenous (pharmacology)
• Chickens (metabolism)
• Glycosylation
• Anti-Inflammatory Agents (pharmacology)