A research team led by Professor Seok-Mook Lee of the Bio-Pharmaceutical Department, College of Science and Technology, Kookmin University (President Jeong Seung-ryul) has developed a new antibody lead compound that can regulate immune responses without side effects and elucidated its mechanism of action.

This antibody is attracting considerable attention because it suppresses the excessive response of T cells, a type of immune cell, without causing the serious side effects that have been a problem with existing treatments. This research was led by Professor Lee Seok-Mook and Ph.D. candidate Yang Ha-Rim of the Department of Applied Chemistry at Kookmin University.

Immune cells in our bodies perform the important function of removing viruses and cancer cells. However, when this function is overactivated, problems such as autoimmune diseases and organ transplant rejection occur, in which normal cells are also attacked. The research team has developed an antibody that can put the brakes on such excessive immune responses.

The newly developed antibody, K108.5, precisely targets CD3ε (CD3 ε), a key protein involved in T cell activation. Unlike existing antibodies, it does not overly stimulate T cells, making it safer with fewer side effects.

The representative CD3ε antibody, ‘Muromonab-CD3 (OKT3),’ excessively stimulates T cells, causing severe side effects such as high fever or ‘cytokine storms,’ which have limited its clinical application. In contrast, K108.5 demonstrates the potential to precisely regulate T cell responses while stabilizing the immune system without such side effects.

The research team utilized phage display technology to select K108.5 from numerous antibody candidates. This antibody binds to a different site (epitope) of the CD3ε protein than existing antibodies, rapidly internalizing the protein into cells and reducing its expression on the T cell surface. This inhibits excessive T cell activation, effectively blocking unnecessary immune responses.

Additionally, the research team confirmed the mechanism of K108.5 by culturing T cells with other immune cells (dendritic cells). The results showed that T cell responses that were overly activated by existing antibodies or dendritic cells were significantly suppressed by K108.5, and markers of immune cell activation and the production of inflammatory substances (cytokines) were also greatly reduced. This suggests that K108.5 has the ability to selectively regulate pathologically overactivated T cells.

Professor Lee, Sukmook stated, “This study is significant as it precisely analyzed the structure and signaling mechanisms of CD3ε, identified the underlying causes of side effects in existing antibody therapies, and proposed a new antibody design strategy to overcome these issues. K108.5 holds high potential to develop into a next-generation immune modulation therapy platform applicable to various fields such as autoimmune diseases, organ transplantation, and cancer treatment.”

This study was published online in July 2025 in the International Journal of Biological Macromolecules (IF 8.5), a leading international academic journal in the fields of biochemistry and antibodies. This journal is internationally recognized as an authoritative publication in the field of therapeutic research based on biomacromolecules.

The research team plans to conduct follow-up studies on the preclinical efficacy and safety of K108.5 to thoroughly evaluate its potential for development as an actual therapeutic agent. This study is expected to serve as an important milestone in the development of new antibody therapies that regulate immune responses.