research
Professor Hak-Sung Kim of Biological Sciences at KAIST publishes a cover article on artificial antibody in "Molecular Therapy".
Repebody-based lung cancer therapeutic drug candidate developed
Repebody-based protein demonstrates the possibility of the development of a new drug
KAIST Biological Sciences Department’s Professor Hak-Sung Kim, in collaboration with Professor Eun-Kyung Cho from the College of Medicine at Chungnam National University, has successfully developed an artificial antibody-based, or repebody, cancer therapeutic candidate. These research results were published as a cover paper of the July edition of Molecular Therapy.
The repebody developed by Professor Kim and his team strongly binds to interleukin-6, a cancer-causing factor. It has also been confirmed that the repebody can significantly inhibit the proliferation of cancer cells in non-small-cell lung cancer animal model.
Numerous multinational pharmaceutical and biotechnology companies have invested astronomical amounts of money in research for the development of protein therapeutics with low side effects and high efficacy. More than 20 kinds of such therapeutics are currently under clinical trials, and over 100 drugs are under clinical demonstration. Among these, the majority is antibody-based therapeutics, and most of the investments are heavily concentrated in this field. However, antibody production cost is very high because it has large molecular weights and complex structural properties, and this makes it difficult to engineer. Consequently, the development costs a great deal of time and money.
In order to overcome the existing limitations of antibody-based therapeutics, Professor Kim and his team have developed a new artificial antibody, or repebody, which was published in Proceedings of the National Academy of Sciences (PNAS) in 2012. Based on this research, they have succeeded in developing a therapeutic candidate for treating non-small-cell lung cancer with a specifically strong cohesion to the cancer-causing factor, interleukin-6.
Interleukin-6 is a crucial substance within the body that is involved in immune and inflammatory-related signals. When abnormally expressed, it activates various carcinogenic pathways and promotes tumor growth and metastasis. Because of its importance, multinational pharmaceutical companies are heavily investing in developing therapeutics that can inhibit the signaling of interleukin-6.
In this study, Professor Kim and his team observed that a repebody consists of repeated modules, and they conceived a module-based affinity amplification technology that can effectively increase the binding affinity with the disease target. The developed therapeutic candidate has been confirmed in cell and animal experiments to show low immunogenicity, as well as to strongly inhibit the proliferation of non-small-cell lung cancer.
Furthermore, by investigating the complex structure of the repebody with interleukin-6, Professor Kim has identified its mechanism, which demonstrated the potential for therapeutic development. The researchers are currently carrying out pre-clinical trials for acquiring permission to perform clinical trials on animals with non-small-cell lung cancer. The repebody can be developed into a new protein drug after demonstrating its safety and efficacy.
Professor Hak-Sung Kim and his team have confirmed that the repebody can be utilized as a new protein drug, and this will be a significant contribution to Korea’s protein drugs and biotechnology industry development.
The research was supported by the Future Pioneer Industry project and sponsored by the Ministry of Science, ICT and Future Planning.
Figure 1. Professor Kim’s article published as the cover article of July edition of Molecular Therapy
Figure 2. Clinical proof of the repebody’s inhibition of cancer growth using animal models