Humanising Antibodies by CDR Grafting

Following the original discovery of the process for making mouse monoclonal antibodies by Kohler and Milstein in 1975 a tremendous amount of effort has been expended to isolate mouse antibodies against specific antigenic targets, creating a huge reservoir of potential therapeutic agents. Unfortunately, the numerous limitations associated with the long term use of mouse monoclonal therapeutic antibodies have been so severe that until recently, very few monoclonal antibodies had been licensed for human use in the intervening time. The major stumbling blocks to their use as therapeutic agents include: • Short serum half life. • Poor utilisation of human effector functions via the mouse constant regions. • Rapid onset of a human anti-globulin response to mouse specific residues — also known as the HAMA (Human Anti-Mouse Antibody) response.