A Polishing Strategy for Removing Impurities in Bispecific Antibody Purification

From Left: Farouq Bin Mahfut, Liew Jia Min, Wang Xinhui, Dr Nattha Ingavat, Dr Zhang Wei and Dr Yang Yuansheng

 

Science

Bispecific antibodies (bsAbs) are emerging as one of the promising biotherapeutic modalities. They allow the binding of two different antigens or epitopes, offering potential therapeutic advantages over the traditional monoclonal antibodies. However, intricate impurity profiles are inherent to both the product and the bioprocess of bsAbs production. Coupled with its high propensity for aggregation, these properties pose considerable challenges in the downstream processing of bsAbs.

In a study to improve bsAb purity, the team discovered that the commonly used cation exchange chromatography for polishing induced more aggregation in all three different bsAbs formats tested. To address these challenges, they developed a mixed-mode chromatography-based method to polish bsAbs and achieved at least 97% product purity while minimising process-related aggregation.

 

Societal Impact

The high aggregation propensity of bsAbs impedes manufacturing productivity. The importance of their development lies in achieving high product purity in downstream processing while minimizing process-induced aggregation. The findings present a promising alternative in bsAbs purification, potentially enhance manufacturing productivity by shortening time and reducing costs for cancer immunotherapy productions.

 

Technical Summary

The study elucidated a polishing strategy for bsAbs, leveraging a mixed-mode medium to achieve products with a minimum of 97% purity and minimal process-related impurities. The optimised process consistently demonstrated excellent aggregate removal and mitigated process-related aggregation. Additionally, the polishing strategy demonstrated the potential in low molecular weight species removal, although further studies are warranted. These findings offer valuable insights for experts in the field, providing essential guidelines for optimizing and advancing bsAb purification processes.

 

References

Ingavat, N., Wang, X., Liew, J. M., Mahfut, F. B., But, K. P., Kok, Y. J., Bi, X., Yang, Y., Shintaro, K., Tsoumpra, M., Zhang, W. (2023). Harnessing ceramic hydroxyapatite as an effective polishing strategy to remove product- and process-related impurities in bispecific antibody purification. Bioresources and Bioprocessing, 10(1), 93. doi:10.1186/s40643-023-00713-9