Simultaneous Humanization and Affinity Optimization of Monoclonal Antibodies

Monoclonal antibodies (MAbs) have broad therapeutic applications in cancer therapy, prevention and treatment of viral infection, immune suppression, etc. However, many well-characterized MAbs are derived from murine sources, and these antibodies have been shown to induce strong immunogenicity when administered into the human body. The ensuring human anti-mouse antibody (HAMA) response consequently can induce fast clearance of administered antibodies from serum resulting in significantly reduced efficacy. In addition, murine MAbs also have weak effector function in human, which is important for certain clinical applications. To overcome these shortcomings, humanization techniques are used to modify nonhuman MAbs for therapeutic use. Humanization can reduce and potentially eliminate the human immune response to administered foreign antibodies. It is a critical step in maximizing the usage of MAbs as therapeutic agents.