Mathematical Modeling of Tumor and Cancer Stem Cells Treated with CAR-T Therapy and Inhibition of TGF-[Formula: see text].

The stem cell hypothesis suggests that there is a small group of malignant cells, the cancer stem cells, that initiate the development of tumors, encourage its growth, and may even be the cause of metastases. Traditional treatments, such as chemotherapy and radiation, primarily target the tumor cells leaving the stem cells to potentially cause a recurrence. Chimeric antigen receptor (CAR) T-cell therapy is a form of immunotherapy where the immune cells are genetically modified to fight the tumor cells. Traditionally, the CAR T-cell therapy has been used to treat blood cancers and only recently has shown promising results against solid tumors. We create an ordinary differential equations model which allows for the infusion of trained CAR-T cells to specifically attack the cancer stem cells that are present in the solid tumor microenvironment. Additionally, we incorporate the influence of TGF-[Formula: see text] which inhibits the CAR-T cells and thus promotes the growth of the tumor. We verify the model by comparing it to available data and then examine combinations of CAR-T cell treatment targeting both non-stem and stem cancer cells and a treatment that reduces the effectiveness of TGF-[Formula: see text] to determine the scenarios that eliminate the tumor.

Modeling the stem cell hypothesis: Investigating the effects of cancer stem cells and TGF-ß on tumor growth.

We propose a mathematical model to describe the interaction of cancer stem cells, tumor cells, and the immune system in order to better understand tumor growth in the presence of cancer stem cells. We consider the system in two scenarios: with no-treatment and with a chemotherapy treatment regimen. We develop a system of differential equations, fit the parameters to experimental data, and perform sensitivity and stability analysis. The model simulations show that the tumor cells grow as predicted with no-treatment and that with chemotherapy, which targets only the tumor cells, the cancer will eventually relapse. As chemotherapy does not target the cancer stem cells, we conclude that the tumor cells recover due to the presence of cancer stem cells.