Antibody drugs now accounting for seven of the top 10 blockbuster sales in the world, have become leading role of pharmaceuticals. In recent years, although new modalities such as nucleic acid and regenerative medicines are attracting attention, the superiority of antibody drugs is considered to continue for a while time. On the other hand, it is difficult to say that Japan’s contribution in this field is convinced, and in order to overcome this situation and create international competitive edge, the development of next-generation antibody based on Japan-origin technologies is an urgent issue. The research project team composed of Kagoshima University (Professor Ito), Tottori University (Professor Kazuki) and Tokyo University of Pharmacy and Life Sciences (Professor Tomizuka), who had long worked on the development of antibody therapeutics as academia or company researchers (Figure 1), invented the idea to create the combined biologics composed of tissue-specifically delivering antibody and biological active protein, based on the noticeable properties of antibodies including high variation, high specificity and in vivo long half-life.
This research project aims to establish tissue-specific delivering antibodies AccumBody by utilizing TC/Phage technology, which combines fully human antibody production technology using TC mice/rats unique to Tottori University, and phage library technology that Kagoshima University specializes in, as shown in Figure 2. By connecting AccumBody and therapeutic agents with site-specific modification method CCAP from Kagoshima University, multifunctional biologics as a new modality of therapeutics originated from Japan is proposed.
The research will be conducted according to the following five items. 1) Development of Multiple Sclerosis therapeutics with brain-delivering antibodies: In addition to developed brain-delivering antibodies (AccumuBrain), new brain-delivering antibodies are isolated by TC/Phage technology. By connecting therapeutic agents to AccumuBrain, development of multifunctional therapeutic drug accumulating to the brain and enhancing regeneration/repair effects on neurons is conducted. 2) Development of therapeutics for inflammatory bowel disease with intestinal-delivering antibodies: In addition to the established antibodies, we develop new intestinal homing antibodies. The generated therapeutic biologics is with main efficacy of intestinal mucosa regeneration and repair. 3) Development of therapeutics for Duchenne muscular dystrophy with muscle-delivering antibodies: The isolation of muscle homing antibodies is carried out by muscle tissue and muscle cells into TC mice/rats. The therapeutic effect of the muscle-AccumBody combined with nucleic acid medicine is evaluated using the established Duchenne muscular dystrophy-disease mouse model. 4) Development of fully human immune mouse with a human complete immune system is also aimed to evaluate the immunogenicity of the biologics. The development of next-generation complete human antibody-producing mice: A human antibody-producing nude mouse can essentially contribute to obtention of AccumBody. 5) Development of next-generation CCAP method: Improvement of CCAP method used for conjugates is aimed.
Through the above, we will achieve the creation of a series of next-generation antibody drugs by new Japan-origin technologies and contribute greatly to enhance international competitiveness in this field of Japan. Finally, the members from the three groups to promote this project are introduced in Figure 3.
Figure 1: Three research groups supporting this project
Figure 2: Development of new modalities from Japan by highly functional antibody drugs as next-generation combined biologics using tissue-delivering antibody, named AccumBody
Figure 3: Project members for Kagoshima University (top), Tottori University (middle) and Tokyo University of Pharmacy and Life Sciences (bottom)