When we are infected with pathogens like viruses or bacteria, our immune system produces proteins named “antibodies”, which recognize the individual pathogens. Antibodies bind specifically to pathogens and inactivate them, or antibodies bound to pathogens become “flags” for the immune system to exclude pathogens. Making use of these properties of antibodies, “therapeutic antibodies” have been developed as drugs for cancer, autoimmune diseases and infectious diseases etc. For example, some therapeutic antibodies bind to the surfaces of tissue cells and these tissue cell-antibody complexes are removed by immune system, and others induce signals in the tissue cells to commit suicide when they bind to the tissue cells. Therapeutic antibodies are highly effective and, as antibodies are proteins naturally produced in our bodies, they are highly safe, which makes them the most successful type of drug these days. However, there are concerns that the discovery of novel lead therapeutic antibodies would be more difficult in the future because of the “exhaustion” of the therapeutic targets and the limited mode of action of antibodies. “Bispecific antibody”, which recognizes two targets simultaneously, is one of the most anticipated formats of the next generation therapeutic antibodies. In fact, some therapeutic bispecific antibodies have been approved which cross-link cancer cells and immune cells, resulting in the killing of the cancer cells by the immune cells. However, the discovery of the bisipecific antibody-based drug candidates requires complicated and laborious experimental processes, prolonging the overall discovery timeline. So far, we have developed an in vitro method to generate monoclonal antibodies, namely the ADLib system, as a platform technology to generate therapeutic lead antibodies rapidly. In this project, utilizing the result of the basic studies on immunoglobulin gene rearrangements and chromosome structure, we are developing a bispecific version of the ADLib system. Our goal is to build a technology that isolates the antigens specific bisopecific clones effectively and rapidly by simple process including cell culturing and magnetic beads selection. We also aim to develop a method to enhance the binding activities of these bispecific antibodies seamlessly using the obtained clones. Through this project, the rapid and effective generation of bispecific antibodies and their optimization will be enabled, accelerating the development of the next generation therapeutic antibodies.