Periodically Pulsed Immunotherapy in a Mathematical Model of Tumor, CD4⁺ T Cells, and Antitumor Cytokine Interactions

Immunotherapy is one of the most recent approaches for controlling and curing malignant tumors. In this paper, we consider a mathematical model of periodically pulsed immunotherapy using CD4⁺ T cells and an antitumor cytokine. Mathematical analyses are performed to determine the threshold of a successful treatment. The interindividual variability is explored by one-, two-, and three-parameter bifurcation diagrams for a nontreatment case. Numerical simulation conducted in this paper shows that (i) the tumor can be regulated by administering CD4⁺ T cells alone in a patient with a strong immune system or who has been diagnosed at an early stage, (ii) immunotherapy with a large amount of an antitumor cytokine can boost the immune system to remit or even to suppress tumor cells completely, and (iii) through polytherapy the tumor can be kept at a smaller size with reduced dosages.