Hyung-Kwon Lim
Head of Antibody Engineering of MOGAM Biotechnology, Research Institute Yongin, Republic of Korea
This presentation will describe a novel platform technology to engineer super-stable human heavy chain variable domain (VH) as an alternative antibody scaffold and its uses for formatting next generation antibodies. Principles of the technology using in vivo protein folding pathway and characterization of the resulting scaffolds will be discussed at the molecular level. In addition, several case studies for the construction of the series of single domain antibody libraries and data from the screening against specific target antigens will be presented.
Why is this presentation important?
Human heavy chain variable domains (VH) are inherently unstable, which limits its biotechnological applications. This presentation will show a first attempt for using in vivo protein folding proof mechanism (Tat pathway) to evolve VH, which is distinct from the conventional heat denatured phage display method. By comparison of its mutational profile and crystal structure between parental and selected VH, we elucidated the hallmarks of stability of VH proteins. These findings should help designing novel next generation antibodies for therapeutic purposes.