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Development of Multi-Specific Antibody-Serum Albumin Fusion Proteins Targeting Multiple Human and Murine CXC (ELR+) Chemokines
Massachusetts Institute of Technology
Antibody
Inflammatory disease
Hit To Lead or Lead Optimization
• Ab binds multiple CXC chemokines to block the CXC inflammatory cascades.
• This technology uses an antibody that promiscuously binds multiple CXC chemokines to block the CXC inflammatory cascades associated with RA. A panel of promiscuous antibodies was developed through three sequential rounds of PCR-mutagenesis and directed evolution by selecting for antibodies with both promiscuous binding tendencies (binding to multiple CXCLs), and high binding affinity against multiple CXCLs.
• The antibodies were then fused to the serum albumin protein, which stabilizes the antibody in circulation and increases the in vivo half-life. The top three antibody hits from this directed evolution scheme blocked receptor activation in response to 2-5 different CXC ligands in vitro.
• The inventors performed proof of concept experiments in an in vivo mouse model of RA that demonstrated a complete resolution of RA disease burden in only 10 days in response to the top candidate antibody.
US20210246199A1
Directed Evolution of Broadly Crossreactive Chemokine-Blocking Antibodies Efficacious in Arthritis. Nature Communications, (2018)
