Mathematical Model for Non-Monotone Dose Response to the PD-L1 Blockade in vitro

We present a model for T-cell re-activation under the action of therapeutic compounds targeting the PD-1/PD-L1 interaction. The effector T cells in the assay express Luciferase upon TCR-mediated activation, which is diminished by the presence of PD-1/PD-L1 interaction provided by co-cultured artificial antigen-presenting cells. Upon PD-L1 blockade with tested compounds added for 6 hours at different dose concentrations, the activation of effector T cells is restored, reflected by increased luminescence signals. The resulting dose response curve is non-monotone due to the existence of two separate and antagonizing effects - specific activation of T cells and unspecific toxicity, observed separately, but also overlapping at a certain range of the compound concentration. A mathematical model is used to estimate the concentration for maximum level of activation and the EC50 concentration. The model presents a mechanism for the temporal change in the activity of the Firefly Luciferase over the course of the experiment as measured by the strength of the luminescent signal based on a system of ODEs. Parameters of the model are estimated from experimental data and are used to estimate the drug concentration corresponding to the maximum level of T-cell activation and the EC50 concentration. This is joint work with Lukasz Skalniak (Department of Organic Chemistry, Faculty of Chemistry, Jagiellonian University, Krakow, Poland). This work was supported by grant DP-05-KOST-13 from FNI, Bulgarian Ministry of Education and Science and by grant 2021/42/E/NZ7/00422 from the National Science Centre, Poland.

Mathematical Model for Non-Monotone Dose Response to the PD-L1 Blockade in vitro

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Peter Rashkov

"Mathematical Model for Non-Monotone Dose Response to the PD-L1 Blockade in vitro"

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