January 23, 2025
Keio University
A research group from Keio University, led by Koichi Ideura (a first-year master's student at the Graduate School of Science and Technology), Associate Professor Yuki Hiruta of the Faculty of Science and Technology, and Senior Assistant Professor Yasuhiro Moriwaki of the Faculty of Pharmacy, has modified the surface of a column packing material for high-performance liquid chromatography with synthetic polymers that mimic the antibody-binding region of protein A. They then evaluated the pH-dependent retention and elution behavior of therapeutic antibodies. The results revealed that this packing material, similar to column packing materials modified with protein A, retains antibodies at a neutral pH and elutes them at an acidic pH. This finding indicates its potential application as a low-cost and highly stable antibody purification method.
The demand for therapeutic antibodies has been increasing in recent years as groundbreaking treatments for cancer and autoimmune diseases. The purification cost of antibodies accounts for about 60% of the total manufacturing cost of therapeutic antibodies, making cost reduction an urgent issue. Furthermore, protein A columns used in conventional purification methods have drawbacks such as low stability and high cost. There are also concerns that elution under low pH conditions may cause a loss of antibody activity. In this study, we mimicked the function of protein A using synthetic polymers, which are less expensive and more stable than proteins, and applied them to antibody purification with operations similar to conventional methods. By mimicking the amino acid sequence of the antibody-binding region of protein A (Z34C) and the function of histidine, an amino acid crucial for binding to antibodies, we imparted a pH-dependent retention and elution behavior to the synthetic polymers, similar to that of protein A columns. Furthermore, we successfully purified antibodies from hybridoma cell culture supernatants with a recovery rate exceeding 80% under mild elution conditions (pH 5). In addition, the material maintained a highly reproducible recovery rate even after 100 consecutive purification cycles and six months of use, confirming its reusability and durability. These results suggest the potential to achieve antibody purification that is less expensive and more durable than conventional methods, while maintaining antibody activity. This technology is expected to contribute significantly to reducing manufacturing costs in the ever-expanding therapeutic antibody market.
The results of this research were published on November 26, 2024, in the American Chemical Society journal " ACS Applied Materials & Interfaces ."
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