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Henry Lowman Director: Antibody Engineering |
"We are interested in understanding molecular recognition and the relationship between protein-protein binding interactions and biological activity. We use structure-based design and molecular diversity techniques to optimize specificity, binding affinities, and kinetics of antibodies, as well as to develop new antibody formats. Phage display and Surface Plasmon Resonance (BIAcore) are key technologies in the group.
Antigen recognition
Antibodies, developed through hybridoma techniques or from naïve-diversity libraries, recognize their cognate antigens through molecular contacts of the variable domains (Fv) with specific sites on the antigen (epitopes) with characteristic binding affinities. We have used structure-based and molecular diversity approaches to alter antibody binding kinetics and affinities. Phage-based affinity maturation led to a high-affinity anti-VEGF Fab antibody (Lucentis® (ranibizumab injection)) for the treatment of age-related macular degeneration, as well as a high-affinity, second-generation antibody currently in development for immunology indications.
Effector functions
In vivo, antibodies may also interact with the immune system through molecular interactions of their constant domains (Fc) with specific receptors that mediate antibody-dependent cytotoxicity, transcytosis and clearance, and phagocytosis. They may also interact with the complement system to mediate cell lysis. We are exploring the in vitro and in vivo consequences of modulating these interactions using phage display and structure-based design in collaboration with Protein Engineering and Pharmacokinetic and Pharmacodynamic Sciences."