Analysis of tumor-immune functional responses in a mathematical model of neoantigen cancer vaccines

被引:5
|
作者
Han, Lifeng [1 ]
Messan, Marisabel Rodriguez [1 ]
Yogurtcu, Osman N. [1 ]
Nukala, Ujwani [1 ]
Yang, Hong [1 ]
机构
[1] US FDA, Ctr Biol Evaluat & Res, Off Biostat & Pharmacovigilance, Silver Spring, MD 20437 USA
关键词
Neoantigen cancer vaccines; Phase plane analysis; Killing rate function;
D O I
10.1016/j.mbs.2023.108966
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Cancer neoantigen vaccines have emerged as a promising approach to stimulating the immune system to fight cancer. We propose a simple model including key elements of cancer-immune interactions and conduct a phase plane analysis to understand the immunological mechanisms of cancer neoantigen vaccines. Analytical results are obtained for two widely used functional forms that represent the killing rate of tumor cells by immune cells: the law of mass action (LMA) and the dePillis-Radunskaya Law (LPR). Using the LMA, our results reveal that a slowly growing tumor can escape the immune surveillance and that there is a unique periodic solution. The LPR offers richer dynamics, in which tumor elimination and uncontrolled tumor growth are both present. We show that tumor elimination requires sufficient number of initial activated T cells in relationship to the malignant cells, which lends support to using the neoantigen cancer vaccine as an adjuvant therapy after the primary tumor is surgically removed or treated using radiotherapy. We also derive a sufficient condition for uncontrolled tumor growth under the assumption of the LPR. The juxtaposition of analyses with these two different choices for the killing rate function highlights their importance on model behavior and biological implications, by which we hope to spur further theoretical and experimental work to understand mechanisms underlying different functional forms for the killing rate.
引用
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页数:10
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