<Figure1> Project research outline
Building the technical foundation for new antibody drugs in 5 areas based on IgG modification technique.
Research and Development Projects Adopted in FY2014
Development of a series of advanced functional antibody drugs using techniques of specific modification to human IgG antibody
Project Leader:Ito Yuji
Professor, Graduate School of Science and Engineering, Kagoshima University
Almost fifty antibody drugs have been developed to treat various diseases. However, the target antigen for many of antibody drugs is limited to the extracellular soluble factors and/or membrane-bound cell surface receptor, and their action is mainly based on the effector functions such as binding inhibition to the receptor of ligand, ADCC (Antibody-dependent cellular cytotoxicity), and CDC (Complement-dependent cellular cytotoxicity). Although new developments have been made in recent years, they are antibody fragment drugs, such as Fab, Nanobodies (VHH) and BiTE (Bispecific T Cell-Engaging Antibody), or ADC (Antibody-Drug Conjugate). We believe that in order to achieve further progress of biotherapeutics, we need to improve and diversify the effector functions of antibody, as well as to further explore new target molecules for antibody therapy to treat the diseases.
This project uses a unique technology of a new peptide reagent that can specifically modify human IgG quickly and efficiently, and aims to create a series of antibody drugs with a wide array of advanced functions by connecting the specific molecules with the effector function to antibody. It also includes the development of antibody drugs against disease-associated target molecules in brain and inner cell which have not been targeted by antibody drugs currently.
The project is jointly conducted by the Ito Research Team of Kagoshima University (project leader: Professor Yuji Ito), Tokyo University of Pharmacy and Life Sciences (project coleader: Professor Yoshio Hayashi), RIKEN center for Molecular Imaging Science (project coleader: Researcher Yosuke Kanayama) and the research team of Kyowa Hakko Kirin Co., Ltd (project coleader: Senior Researcher Nobuaki Takahashi). The Ito Research Team has enough experience and knowledge's in designing specific peptide and antibody to target molecules by phage display library. By this technique, they will develop molecules (peptide and antibody) that have new effector functions to target inner cell and brain. The Hayashi Research team in Tokyo University of Pharmacy and Life Sciences is skilled in peptide mimetics and development of anticancer drugs based on peptide chemistry. They will establish a new chemical modification system to improve the functions of antibodies such as ADC. The Kanayama Research Team of RIKEN who has newly joined to the project focuses on the research of in vivo imaging using antibody radionuclide conjugate produced in this project. The Takahashi Research Team of Kyowa Hakko Kirin Co., Ltd will evaluate the efficacy of the developed antibodies from the point of view as a development company of antibody drugs. They will also develop new antibodies directed to areas that have not been targeted by current antibody drugs. The teams work collaboratively to establish the technical foundation for the development of a variety of new advanced antibody drug.
The current market of antibody drugs is dominated by foreign companies, although only a few of antibody drugs are made by Japanese companies. In order to overcome the situation, industry, academia and government should cooperate – academia creates new pharmaceutical candidates generated by new technologies and concepts; government supports to cultivate them; industry gives them a concrete shape for the products. We hope to lead this project to success as an example of Japanese style's new innovation cycle.
<Figure2> Members of Research Project
From left: Professor Hayashi (project coleader, Tokyo University of Pharmacy and Life Sciences), Professor Ito (project leader, Kagoshima University), Senior Researcher Takahashi (project coleader, Kyowa Hakko Kirin Co., Ltd.)