MATHEMATICAL MODELING OF IN-VIVO TUMOR-IMMUNE INTERACTIONS FOR THE CANCER IMMUNOTHERAPY USING MATURED DENDRITIC CELLS

摘要

To develop an anticancer drug, the mathematical models are nowadays indispensable because of complex immunological mechanisms defying with high experimentation costs as well as a large number of parameters. Based on immunological theories and vision of experimentation data, a simple and sufficient compartment model is designed that can accurately interpret and predict the effects of dendritic cell (DC)-based immunotherapy in accordance with experimentation data. The model includes effector cells, regulatory T cells, helper T cells, and DCs. A new key feature is the inclusion of immunotherapy with DCs matured with different materials. All the parameters of the model have been optimally obtained by fitting the experimental data using genetic algorithm. The proposed model has been used to predict a near-optimal pattern that minimizes tumor size after vaccination. This pattern has been validated by carrying out the associated in-vivo experimentation. The model recommends maturation materials and doses that activate a small amount of Treg in the early days and a large Th1/Treg ratio in the next days. The performance of the model compared with the previous study was shown to be superior, both qualitatively and quantitatively.