Computational Simulations for Investigating the Interaction between CD8+ CAR T Cells and the EGFRvIII Receptor in Glioblastoma

Chimeric Antigen Receptor T-cells, or CAR T-cells, are T cells that have undergone genetic engineering to destroy cancer cells. Recently, CAR T-cell therapy specifically targeting EGFRvIII receptors of glioblastoma cells has been developed. Computer Aided Drug Design (CADD) has been an indispensable tool in the intricate drug discovery process. In the current investigation, we have performed computational simulations, specifically molecular docking and molecular dynamics, to find the interactions of CD8+ CAR T-cells to the overexpressed EGFRvIII in glioblastoma. The simulations show that they form strong interactions at the interface. In addition, their binding was further confirmed by using a graph neural network. The CD8EGFRvIII binding affinity was computed using the Prodigy software. We propose that the specificity of CD8 towards EGFRvIII is attributed to the unique structure of EGFRvIII. The truncated extracellular domain of EGFRvIII creates a specific site that facilitates direct binding of CD8. This binding interaction is not feasible with wild-type EGFR (wt-EGFR), thus enabling CD8 CAR T-cells to target glioblastoma cells while sparing normal cells selectively. These results will help understand the binding mechanism of two receptors and will aid in developing novel CAR-T-cell therapy against the disease.