Antibody engineering

The laboratory has considerable experience engineering recombinant antibodies for therapeutic and diagnostic applications. Common techniques include development of mouse-human chimeric antibodies and affinity enhancement of antibody variable regions.

Many of our monoclonal antibodies (mAbs) target polysaccharides and proteins that are exposed on the surface of bacteria and fungi. We have determined that some of these mAbs provide passive protection in animal models of infection. Eventually, the therapeutic use of these mAbs requires replacement of the mouse antibody constant regions with human antibody constant regions. This conversion essentially eliminates the human anti-mouse antibody (HAMA) response that develops in patients that are administered mouse mAbs.

Production of high affinity antibodies is essential for an effective immunodiagnostic or immunotherapeutic. Therefore the laboratory has developed the ability to affinity enhance antibodies by phage display. The technique involves randomly mutating variable regions at specific sites to isolate antibodies with improved binding to target antigens. The resulting recombinant antibodies may be more potent when used as an immunotherapeutic or more sensitive when used as a component of an immunodiagnostic.

The laboratory has the ability to perform all of the molecular biology techniques needed to produce recombinant antibodies. The OptiCHO™ Express Kit is used for cloning and increased expression of recombinant antibodies in DHFR-deficient Chinese Hamster Ovary (CHO) cells propagated in WAVE bioreactors™. Recombinant antibodies are then affinity purified over protein A and G columns.