Study of dose-dependent combination immunotherapy using engineered T cells and IL-2 in cervical cancer.

• A mathematical model for combination therapy using engineered T cells and IL-2. • The results provide a TCR T cell dose window for a successful therapy. • Combination therapy does not always provide a better outcome. Adoptive T cell based immunotherapy is gaining significant traction in cancer treatment. Despite its limited efficacy so far in treating solid tumors compared to hematologic cancers, recent advances in T cell engineering render this treatment increasingly more successful in solid tumors, demonstrating its broader therapeutic potential. In this paper we develop a mathematical model to study the efficacy of engineered T cell receptor (TCR) T cell therapy targeting the E7 antigen in cervical cancer cell lines. We consider a dynamical system that follows the population of cancer cells, TCR T cells, and IL-2 treatment concentration. We demonstrate that there exists a TCR T cell dosage window for a successful cancer elimination that can be expressed in terms of the initial tumor size. We obtain the TCR T cell dose for two cervical cancer cell lines: 4050 and CaSki. Finally, a combination therapy of TCR T cell and IL-2 treatment is studied. We show that certain treatment protocols can improve therapy responses in the 4050 cell line, but not in the CaSki cell line. [ABSTRACT FROM AUTHOR]