Enhancing immunotherapies: Insights from the mathematical modelling of a microfluidic device

AlexisFarman

UCL (University College London)

"Enhancing immunotherapies: Insights from the mathematical modelling of a microfluidic device"

A pivotal aspect of developing effective immunotherapies for solid tumors is the robust testing of product efficacy inside in vitro platforms.Collaborating with an experimental team that developed a novel microfluidic device at Children’s National Hospital (CNH), we developed a mathematical model to investigate immune cell migration and cytotoxicity within the device. Specifically, we study Chimeric Antigen Receptor (CAR) T-cell migration inside the channels, treating the cell as a moving boundary driven by a chemoattractant concentration gradient. The chemoattractant concentration is governed by two partial differential equations (PDEs) that incorporate key geometric elements of the device. We examine the motion of the cell as a function of its occlusion of the channel and find that certain cell shapes allow for multiple cells to travel inside the channel simultaneously. Additionally, we identify parameter regimes under which cells clog the channel, impairing their movement. All our findings are validated against experimental data provided by CNH. We integrate our model results into a broader model of the device, which also examines the cytotoxicity of CAR T-cells. This provides a tool for distinguishing experimental artifacts from genuine CAR T-cell behavior. This collaboration enabled the team at Children’s National Hospital to refine experimental conditions and uncover mechanisms enhancing CAR T-cell efficacy. [1] D Irimia, G Charras, N Agrawal, T Mitchison, M Toner, Polar stimulation and constrained cell migration in microfluidic channels,, Lab on a Chip 7 (12), 1783-1790
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