Reinforcement learning‐guided control strategies for CAR T‐cell activation and expansion

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Autori principali: Sakib Ferdous, Ibne Farabi Shihab, Ratul Chowdhury, Nigel F. Reuel
Natura: Artículo Open Access
Pubblicazione: Wiley 2024
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author Sakib Ferdous
Ibne Farabi Shihab
Ratul Chowdhury
Nigel F. Reuel
author_facet Sakib Ferdous
Ibne Farabi Shihab
Ratul Chowdhury
Nigel F. Reuel
Sakib Ferdous
Ibne Farabi Shihab
Ratul Chowdhury
Nigel F. Reuel
collection Wiley Open Access
contents Reinforcement learning‐guided control strategies for CAR T‐cell activation and expansion Sakib Ferdous Ibne Farabi Shihab Ratul Chowdhury Nigel F. Reuel Biotechnology and Bioengineering AbstractReinforcement learning (RL), a subset of machine learning (ML), could optimize and control biomanufacturing processes, such as improved production of therapeutic cells. Here, the process of CAR T‐cell activation by antigen‐presenting beads and their subsequent expansion is formulated in silico. The simulation is used as an environment to train RL‐agents to dynamically control the number of beads in culture to maximize the population of robust effector cells at the end of the culture. We make periodic decisions of incremental bead addition or complete removal. The simulation is designed to operate in OpenAI Gym, enabling testing of different environments, cell types, RL‐agent algorithms, and state inputs to the RL‐agent. RL‐agent training is demonstrated with three different algorithms (PPO, A2C, and DQN), each sampling three different state input types (tabular, image, mixed); PPO‐tabular performs best for this simulation environment. Using this approach, training of the RL‐agent on different cell types is demonstrated, resulting in unique control strategies for each type. Sensitivity to input‐noise (sensor performance), number of control step interventions, and advantages of pre‐trained RL‐agents are also evaluated. Therefore, we present an RL framework to maximize the population of robust effector cells in CAR T‐cell therapy production. 10.1002/bit.28753 http://onlinelibrary.wiley.com/termsAndConditions#am
doi_str_mv 10.1002/bit.28753
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spellingShingle Reinforcement learning‐guided control strategies for CAR T‐cell activation and expansion
Sakib Ferdous
Ibne Farabi Shihab
Ratul Chowdhury
Nigel F. Reuel
Biotechnology and Bioengineering
Reinforcement learning‐guided control strategies for CAR T‐cell activation and expansion Sakib Ferdous Ibne Farabi Shihab Ratul Chowdhury Nigel F. Reuel Biotechnology and Bioengineering AbstractReinforcement learning (RL), a subset of machine learning (ML), could optimize and control biomanufacturing processes, such as improved production of therapeutic cells. Here, the process of CAR T‐cell activation by antigen‐presenting beads and their subsequent expansion is formulated in silico. The simulation is used as an environment to train RL‐agents to dynamically control the number of beads in culture to maximize the population of robust effector cells at the end of the culture. We make periodic decisions of incremental bead addition or complete removal. The simulation is designed to operate in OpenAI Gym, enabling testing of different environments, cell types, RL‐agent algorithms, and state inputs to the RL‐agent. RL‐agent training is demonstrated with three different algorithms (PPO, A2C, and DQN), each sampling three different state input types (tabular, image, mixed); PPO‐tabular performs best for this simulation environment. Using this approach, training of the RL‐agent on different cell types is demonstrated, resulting in unique control strategies for each type. Sensitivity to input‐noise (sensor performance), number of control step interventions, and advantages of pre‐trained RL‐agents are also evaluated. Therefore, we present an RL framework to maximize the population of robust effector cells in CAR T‐cell therapy production. 10.1002/bit.28753 http://onlinelibrary.wiley.com/termsAndConditions#am
title Reinforcement learning‐guided control strategies for CAR T‐cell activation and expansion
topic Biotechnology and Bioengineering
url https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/bit.28753