A novel monoclonal antibody cross-reactive with both human and mouse alpha9 integrin useful for therapy against rheumatoid arthritis.

The present study introduces a novel monoclonal anti-alpha9 integrin antibody (MA9-413) with human variable regions, isolated by phage display technology. MA9-413 specifically binds to both human and mouse alpha9 integrin by recognizing a conserved loop region designated as L1 (amino acids 104-122 of human alpha9 integrin). MA9-413 inhibits human and mouse alpha9 integrin-dependent cell adhesion to ligands and suppresses synovial inflammation and osteoclast activation in a mouse model of arthritis. This is the first monoclonal anti-alpha9 integrin antibody that can react with and functionally inhibit both human and mouse alpha9 integrin. MA9-413 allows data acquisition both in animal and human pharmacological studies without resorting to surrogate antibodies. Since MA9-413 showed certain therapeutic effects in the mouse arthritis model, it can be considered as a useful therapy against rheumatoid arthritis and other alpha9 integrin-associated diseases.