Mathematical model of chimeric anti-gene receptor (CAR) T cell therapy with presence of cytokine. (English) Zbl 1406.92318

Summary: In this paper, we reconstruct a mathematical model of therapy by CAR T cells for acute lymphoblastic leukemia (ALL) With injection of modified T cells to body, then some signs such as fever, nausea and etc appear. These signs occur for the sake of cytokine release syndrome (CRS). This syndrome has a direct effect on result and satisfaction of therapy. So, the presence of cytokine will be played an important role in modelling process of therapy (CAR T cells). Therefore, the model will include the CAR T cells, B healthy and cancer cells, other circulating lymphocytes in blood, and cytokine. We analyse stability conditions of therapy. Without any control, the dynamic model evidences sub-clinical or clinical decay, chronic destabilization, singularity immediately after a few hours and finally, it depends on the initial conditions. Hence, we try to show by which conditions, therapy will be effective. For this aim, we apply optimal control theory. Since the therapy of CAR T cells affects on both normal and cancer cell; so the optimization dose of CAR T cells will be played an important role and added to system as one controller \( u_{1} \). On the other hand, in order to control of cytokine release syndrome which is a factor for occurrence of singularity, one other controller \( u_{2} \) as tocilizumab, an immunosuppressant drug for cytokine release syndrome is added to system. At the end, we apply method of Pontryagin’s maximum principle for optimal control theory and simulate the clinical results by Matlab (ode15s and ode45).


92C50 Medical applications (general)
49N90 Applications of optimal control and differential games


Full Text: DOI


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