Program

Oral Sessions

Day 4, May 18（Fri.）　09:00-09:20　Room C (Seiun 2)

4C-O1-P-0900　　PDF

In vitro Affinity Maturation of Catalytic Antibodies against Transition-state Analogues

(Osaka Pref. Univ.)
^oIluo Fujii

During in vitro affinity maturation using phage display technology, an antibody is subjected to mutagenesis and selection (bio-panning) with the hope that an antibody with “improved” affinity lies near the parent antibody in sequence space. However, it has a critical technical limitation. In bio-panning, phage particles with high affinity antibodies remain stuck on a screening plate after the washing and elution steps. Since the first-generation antibodies elicited by immunization have already acquired strong affinity against the antigens, it is quite difficult to for bio-panning to discriminate among many phages with high affinities and isolate phages with “improved” affinities. To overcome this limitation, various attempts have been performed and reported. Here, we demonstrate a novel approach to take a detour to avoid the limitation. In the detouring method, affinities of antibodies are temporarily decreased, and then increased by phage-displayed technology. We successfully increased the affinity of antibody 6D9 to improve the catalytic activity. This method is also expected to apply for antibody drugs to improve the affinities and the biological activities.