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. 2024 May;121(5):1569-1582.
doi: 10.1002/bit.28669. Epub 2024 Feb 19.

Bayesian cell therapy process optimization

Evan Claes  1   2 , Tommy Heck  1 , Kathleen Coddens  1 , Maarten Sonnaert  1 , Jan Schrooten  1 , Jan Verwaeren  2
Affiliations

Bayesian cell therapy process optimization

Evan Claes et al. Biotechnol Bioeng. 2024 May.

Abstract

Optimizing complex bioprocesses poses a significant challenge in several fields, particularly in cell therapy manufacturing. The development of customized, closed, and automated processes is crucial for their industrial translation and for addressing large patient populations at a sustainable price. Limited understanding of the underlying biological mechanisms, coupled with highly resource-intensive experimentation, are two contributing factors that make the development of these next-generation processes challenging. Bayesian optimization (BO) is an iterative experimental design methodology that addresses these challenges, but has not been extensively tested in situations that require parallel experimentation with significant experimental variability. In this study, we present an evaluation of noisy, parallel BO for increasing noise levels and parallel batch sizes on two in silico bioprocesses, and compare it to the industry state-of-the-art. As an in vitro showcase, we apply the method to the optimization of a monocyte purification unit operation. The in silico results show that BO significantly outperforms the state-of-the-art, requiring approximately 50% fewer experiments on average. This study highlights the potential of noisy, parallel BO as valuable tool for cell therapy process development and optimization.

Keywords: Bayesian optimization; cell therapy; counterflow cell centrifugation; process development; process optimization.

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References

REFERENCES

    1. Abou‐el‐Enein, M., Elsallab, M., Feldman, S. A., Fesnak, A. D., Heslop, H. E., Marks, P., Till, B. G., Bauer, G., & Savoldo, B. (2021). Scalable manufacturing of CAR T cells for cancer immunotherapy. Blood Cancer Discovery, 2(5), 408–422.
    1. Abraham, E., Trainor, N., Ostrout, N., & Hewitt, M. (2021). Cell therapy products are revolutionizing multiple therapeutic areas; to maintain this pace of innovation, manufacturing solutions must adapt. Current Opinion in Biomedical Engineering, 20, 2468–4511.
    1. Bader, J., Narayanan, H., Arosio, P., & Leroux, J. C. (2023). Improving extracellular vesicles production through a Bayesian optimization‐based experimental design. European Journal of Pharmaceutics and Biopharmaceutics, 182, 103–114.
    1. Balandat, M., Karrer, B., Jiang, D., Daulton, S., Letham, B., Wilson, A. G., & Bakshy, E. (2020). BoTorch: A framework for efficient Monte‐Carlo Bayesian optimization. Advances in Neural Information Processing Systems, 33, 21524–21538.
    1. Bashokouh, F., Abbasiliasi, S., & Tan, J. S. (2019). Optimization of cultivation conditions for monoclonal IgM antibody production by M1A2 hybridoma using artificial neural network. Cytotechnology, 71(4), 849–860.

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