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

被引:7
|
作者
Cho, Heyrim [1 ]
Wang, Zuping [2 ]
Levy, Doron [2 ,3 ]
机构
[1] Univ Calif Riverside, Dept Math, Riverside, CA 92521 USA
[2] Univ Maryland, Dept Math, College Pk, MD 20742 USA
[3] Univ Maryland, Ctr Sci Computat & Math Modeling CSCAMM, College Pk, MD 20742 USA
基金
美国国家科学基金会;
关键词
Adoptive T cell transfer; TCR T cells; IL-2; treatment; Combination cancer therapy; Mathematical oncology; TIME-DELAY MODEL; IMMUNE-SYSTEM; MATHEMATICAL-MODEL; PARAMETER-ESTIMATION; DYNAMICS; TUMORS; RECEPTOR; THERAPY; CHEMOTHERAPY; HELPER;
D O I
10.1016/j.jtbi.2020.110403
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
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. (C) 2020 Elsevier Ltd. All rights reserved.
引用
收藏
页数:8
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