Researchers in South Korea have developed a technology that can treat cancer by breaking down proteins used by cancer cells to evade immune attacks.
A research team led by Professor Yujahyeong from the Ulsan National Institute of Science and Technology (UNIST) announced on the 23rd that they developed a complex assembly technology that breaks down proteins used by cancer to evade the immune system. The research results were published on the 3rd in the international journal Advanced Science.
Cancer cells produce the protein PD-L1 in greater quantities than normal cells and display it on their surface. Thanks to this protein, which sends ‘do not attack’ signals to immune cells, cancer cells can rapidly proliferate while evading the human immune surveillance system.
The research team developed a technology based on the compound 'acetazolamide' that can selectively break down the PD-L1 of cancer cells. Acetazolamide binds to the enzyme 'CAIX', which is primarily distributed on the surface of cancer cells, forming a protein nano complex and pulling immune evasion proteins like PD-L1 into the cell. The nano complex that enters the cell is recognized as an abnormal protein and is degraded in the lysosome, the cell's cleaning factory. As CAIX enzyme is almost absent in normal cells, this reaction occurs only in cancer cells.
Cancer cells that have lost the PD-L1 protein become targets for immune cells. In animal experiments using mice, the cancer size in the group injected with the nano complex was reduced to less than half, and the PD-L1 protein also significantly decreased.
Previously, there were molecules that broke down proteins aiding cancer cells in evading the immune system. However, they were too large to enter the cell effectively or were too complex in structure, making design and synthesis challenging. This research pushed beyond these limits by enabling the complexes to assemble themselves within the body.
Professor Yujahyeong noted, “This is a new form of targeted protein degradation technology that surpasses the limitations of existing technologies. In the future, it could be combined with immune anticancer drugs or applied to various hard-to-treat solid tumors.”
References
Advanced Science (2025), DOI: https://doi.org/10.1002/advs.202503134