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From Left: Dr Zhang Wei, Dr Qiu Beiying, Corrine Wan, Hoi Kong Meng, Dr Sean Chia, Dr Ian Walsh, Dr Ho Ying Swan, Dr Zach Pang Kuin Tian and Dr Yang Yuansheng

 

Science

Despite their therapeutic potential, the development and manufacturing of antibodies (Abs) remains challenging. In particular, during the production process, Abs are often exposed to highly destabilizing conditions, which causes antibody molecules to form unwanted clumps – a phenomenon known as aggregation. In this work, we aim to measure and understand the rates of antibody aggregation, and discover various mechanisms of how they can occur with different stress conditions related to manufacturing.

 

Societal Impact

Assessing antibody aggregation is a regulatory requirement for biotherapeutics. Hence, such insights and models that we have developed in this study can be used to predict the stability of new antibody candidates. It can also pave the way to developing new approaches, especially in antibody engineering and formulations, to design for more stable and effective drugs in the future.

 

Technical Summary

In this work, we investigated the molecular mechanisms of antibody aggregation via thermal and pH stress conditions. Through a combination of experimental measurements monitoring the rate of monomer loss and the size of aggregates formed, and theoretical modelling of these data, we propose a kinetic model that describes quantitatively the microscopic mechanisms of aggregation induced/promoted by these stress conditions.

This approach has potential applications in the quantitative assessment of aggregation propensity for antibody candidates, particularly when conducting accelerated stability studies.

 

References

Meng, Hoi Kong, et al. "Thermal and pH stress dictate distinct mechanisms of monoclonal antibody aggregation." International Journal of Biological Macromolecules 282 (2024): 136601.