Enhancing CAR-T Immunotherapy to Attack Both Tumor and Cancer Stem Cells

The stem cells 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 ODE 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-Beta which has a both a regulatory and promotion effect on the growth of the tumor. We verify the model by comparing it to available data and then examine different immunotherapy treatments that attack the tumor cells, stem cells, and both.