Computational Analysis of IL-13Rα2 Specific CAR T-Cells in Glioblastoma Multiforme (GBM)

Glioblastoma Multiforme (GBM) is the most aggressive malignancy in the brain or spinal cord astrocytes. GBM makes up nearly all malignant primary brain tumors. Interleukin-13 receptor subunit alpha-2 (IL-13Rα2) is a monomeric receptor overexpressed in most GBM cases. Chimeric Antigen Receptor (CAR) T-cells have exhibited excellent anti-tumoral activity against GBM and other cancer types. Recently, GBM-specific monoclonal antibodies containing CAR T-cell targeting IL-13Rα2 have been created. We hypothesize that to be a GBM-specific CAR T-cell, the CAR should bind to a specific binding region of the IL-13Rα2 receptor. In the current research, we have studied the interactions between antibodies (located on the CAR's surface) and IL-13Rα2 by performing molecular docking simulations. AlphaFold 3 was used to predict the structure of the receptor, and molecular docking simulations using HDOCK2.4 were performed. The GrASP web server suggests that the druggable/binding site on the receptor is on domain 2, and the antibody also binds to this spot. A total of 15 antibodies were evaluated using the following criteria to determine the most suitable binding antibodies: Initially, a visual inspection of IL-13Rα2-antibody complexes was conducted. Subsequently, the binding energy of each IL-13Rα2-antibody interaction was calculated. Finally, the number of hydrogen bonds was analyzed. Based on the above analysis, antibody 1F8T showed the most promising properties and could be used for CAR development. This study will significantly contribute to developing novel antibody-based CAR T therapy for GBM by providing a deeper understanding of the receptor-antibody binding mechanism via computational simulations.