Tailoring Natural Effector Functions: Antibody Engineering Beyond Humanization

A large number of new biological drugs in clinical development from the biotechnology industry are based on recombinant antibodies. The Food and Drug Administration (FDA) has recently approved several of these drugs including reagents against cancer (1 ,2 ), transplant rejection (3 ), rheumatoid arthritis, and Crohn’s diseases (4 ,5 ) as well as antiviral prophylaxis (6 ). At present 30% of all biological proteins in application for FDA approvals are recombinant antibodies. Some are based on fusions of murine variable regions with human constant region, called chimeric antibodies. Others are more sophisticated being “humanized” from their mouse monoclonal parent molecule, whereas more recently full human antibodies from phage antibody libraries have been generated (7 ).