Simulations from "Mechanistic computational modeling of monospecific and bispecific antibodies targeting interleukin-6/8 receptors"

IL6R/IL8R Antibody Binding Model Code

Christina M.P. Ray, Huilin Yang, Jamie B. Spangler, Feilim Mac Gabhann

This dataset contains all simulation output files generated for the article "Mechanistic computational modeling of monospecific and bispecific antibodies targeting interleukin-6/8 receptors". The model is comprised of a coupled set of ordinary differential equations (ODEs) where each individual ODE describes one molecule (antibody or receptor) or molecular complex (antibody + receptor). The terms in the ODEs represent each binding interaction (binding and unbinding processes) in the system.

The code for the binding model and for the analysis and visualization results is available on GitHub at christyray/bispecific-binding-model.

Specific Simulations

The .csv and  .rds files in the correspond to the results from the simulations performed for the article "Mechanistic computational modeling of monospecific and bispecific antibodies targeting interleukin-6/8 receptors". These files can be read into R using the import_data() function included in the GitHub repository.

The id files contain simulation IDs to link the molecule concentrations (yin) and parameter values (params) with the simulation results (out). When applicable, the norm files contain normalized simulation output, and the occupied files contain receptor fractional occupancy values calculated from the simulation output.

optimization: Optimization of binding rate constants (association and dissociation) to experimental in vitro flow cytometry data; results displayed in Figure 2

binding-curve: Model simulations using the best-fit parameter set for comparison to the experimental data used to fit the model parameters; results displayed in Figure 3

compare-opt: Model simulations using each of the optimized parameter sets; results displayed in the Supplemental Information

time: Simulations of antibody binding dynamics over time; results displayed in Figure 4

concentration: Simulations with varying antibody concentrations and receptor expression levels; results displayed in Figure 5

monovalent: Simulations restricted to monovalent antibody binding only; results displayed in Figure 6

compare-ab and compare-recep: Simulations of both the bispecific antibody BS1 and the combination of monospecific antibodies tocilizumab and 10H2 for comparsion; results displayed in Figure 7

local and global: Local and global univariate sensitivity analyses; results displayed in Figure 8

References

H. Yang, M. N. Karl, W. Wang, B. Starich, H. Tan, A. Kiemen, A. B. Pucsek, Y.-H. Kuo, G. C. Russo, T. Pan, E. M. Jaffee, E. J. Fertig, D. Wirtz, and J. B. Spangler. Engineered bispecific antibodies targeting the interleukin-6 and -8 receptors potently inhibit cancer cell migration and tumor metastasis. Molecular Therapy, 30(11):3430–3449, Nov. 2022. doi:10.1016/j.ymthe.2022.07.008