Simulation-Based Software Modeling of CAR T Cell Therapy Efficacy Against Solid Malignant Tumors

Abstract

Genetically engineered T cells with Chimeric Antigen Receptors, CAR T cells, are a revolutionary immunotherapy used to treat advanced blood cancers. The purpose of this experiment was to model the destruction process of tumor cells with CAR T cell therapy using Complexity and Organized Behaviour Within Environmental Bounds (COBWEB), an agent-based simulation software. We designated parameter values for abiotic factors, agents (i.e. tumor cells, T cells) and the general environment in our immunotherapy simulation model to illustrate the interactions between tumor cells and cytotoxic components, which described the binding of innate CD8+ T cells or CAR T cells to tumor antigens. The models were used to observe and comparatively analyze the rate of destruction of a solid tumor by CAR T cells and innate CD8+ T cells. The solid tumor developed in a circular island for 60 ticks, representing days; innate CD8+ or CAR T cells were then able to infiltrate the island and the tumor cell population was monitored over 500 days. The CAR T cells exhibited a significantly powerful, efficient immune response against a general solid tumor relative to the innate CD8+ T cells, yet relapse occurred in both models albeit to a lesser extent with CAR T cells. However, further investigations are required to adequately simulate the side effects and realistically-limiting factors of CAR T cell therapy. Similar comparative analyses may help measure and compare the potency of the immune response of CAR T cells compared to standard, or lack of, treatments.