Utilizing the CARRGO Model to Compare the Efficacy of HER2- and EGFR- Targeting CAR-NK Cells on Glioblastoma

Glioblastoma is the most common tumor in the central nervous system, and diagnosed patients have a life expectancy of just 15 months. Due to the lack of effective treatments, new therapies, such as chimeric antigen receptor modified natural killer cells (CAR-NKs), are being investigated. These cells are designed to attack cells with a specific antigen target, helping increase treatment specificity. Mathematical models can be used to evaluate the effectiveness of certain treatments and inform the best administration methods for them. Due to the novelty of CAR-NKs, few models accurately describe their actions. The CARRGO model is a mathematical model used to describe the kinetics of CAR-T cells on glioblastoma. Thus, the purpose of this experiment was to evaluate the use of CARRGO as a model for CAR-NKs and compare the effectiveness of HER2 and EGFR targeting CAR-NKs on glioblastoma. It was hypothesized that CARRGO would show that the highest dose of HER2 targeting CAR-NKs would have the greatest impact on the growth of the tumor because of the lowered rate of exhaustion as a result of the higher dose and the higher specific lysis of the CAR-NK cells observed in preclinical studies. Data was collected from preclinical studies and entered into the model. The model showed that HER2 targeting CAR-NKs at the highest dose were the most effective at decreasing tumor load, but the model was insensitive to certain parameter adjustments and had unrealistic data that indicated the need for more accurate models.