Information: NIBIO
Production of "Epitope region-bridging biparatopic antibody" -Improving the functionality of TNFR2 antagonist through 1:1 binding design-
Nov. 1, 2023
A group of scientists in National Institutes of Biomedical Innovation, Health and Nutrition (hereinafter referred to as "NIBIOHN"), Kyoto University, Osaka University, and the University of Tokyo has successfully created a biparatopic antibody (BpAb) that exhibits outstanding functionality as a receptor function inhibitor (antagonist) for tumor necrosis factor receptor type 2 (TNFR2).
BpAb is an artificial bispecific antibody that has been engineered to bind to two different antibody-binding regions (epitope regions) on a single target molecule that cannot be accessed simultaneously by natural antibodies. Natural antibodies with the ligand blocking activity (antagonist function) inevitably shows the weak level of undesired receptor-stimulating activity (agonist function). The undesired effects were concerned for the potential side effects. In this research, the research team led by Dr. Hiroki Akiba, Dr. Satoshi Nagata, and Dr. Kouhei Tsumoto successfully produced a BpAb that binds to TNFR2 in a 1:1-manner, eliminating the agonist function, thereby functions as an excellent antagonist. The unique binding mode was confirmed using cryo-electron microscopy. TNFR2 is known to be involved in suppressing tumor immunity through activation of regulatory T cells. Therefore, the antagonist BpAb is expected to be developed as a therapeutic drug for cancer treatment.
This technology is expected to be applied widely to other receptors and to promote the development of highly functional antibody drugs.
The results of this research were published online in Communications Biology on September 27, 2023.
Website: https://www.nature.com/articles/s42003-023-05326-8
Please click here for the detail.