Glioblastoma (GBM) is a highly aggressive and treatment-resistant primary brain tumor. Despite ongoing advances in clinical research, current therapies provide only limited survival benefits, underscoring the need for more effective treatment strategies. Recent progress in immunotherapy has introduced new therapeutic possibilities, with several agents now under investigation for GBM. Among these, chimeric antigen receptor (CAR) T-cell therapy, which targets tumor-specific antigens, has shown promise across various solid tumors, including high-grade gliomas. In parallel, oncolytic viruses (OVs), engineered to selectively infect and replicate within tumor cells, can induce direct tumor lysis and stimulate anti-tumor immune responses. In this work, we develop a mathematical model based on SIR-type dynamics to study the interactions between GBM cells, CAR T cells, and OVs. The model is parametrized and validated using real-time in vitro killing assay data and flow cytometry from experiments with a patient-derived GBM cell line. Our analysis provides novel insights into the kinetics of CAR T-cell and OV activity and the therapeutic effects of their combination, revealing potential synergies and offering guidance for optimizing dual-agent treatment strategies. This is a joint work in collaboration with A. Xella (Moffitt Cancer Center), R. Woodall (City of Hope), K. Cassady (Nationwide Children’s Hospital Columbus), S. Branciamore (City of Hope), C. Brown (City of Hope), and R. Rockne (City of Hope).