Overview
- Published in Nature Communications, the study describes two antibodies, C01 and C04, that specifically inhibit the high-affinity IgG receptor FcγRI.
- Using a UMAB immunization strategy with phage display, the team overcame a decades-long hurdle to generate Fab-only, Fc-silent binders to the receptor’s IgG site.
- Crystal structure data show C01 binds within the EC2 IgG-binding pocket, making its binding mutually exclusive with IgG.
- Quantitative assays report higher affinity than human IgG, displacement of roughly 60% of pre-bound immune complexes, and up to 90% blocking of new binding.
- In vitro rheumatoid arthritis assays and an in vivo ITP mouse model demonstrated suppressed immune-complex activity and reduced platelet loss, and the patented antibodies now advance toward affinity maturation and humanization.