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

被引:8
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
相关论文
共 50 条
[31]   Novel cellular immunotherapy using NKG2D CAR-T for the treatment of cervical cancer [J].
Zhang, Yan ;
Li, Xing ;
Zhang, Jun ;
Mao, Lin .
BIOMEDICINE & PHARMACOTHERAPY, 2020, 131
[32]   Low-Dose IL-2 Treatment Affords Protection against Subarachnoid Hemorrhage Injury by Expanding Peripheral Regulatory T Cells [J].
Dong, Guoping ;
Li, Cong ;
Hu, Quan ;
Wang, Yuan ;
Sun, Jingyi ;
Gao, Feng ;
Yang, Mingfeng ;
Sun, Baoliang ;
Mao, Leilei .
ACS CHEMICAL NEUROSCIENCE, 2021, 12 (03) :430-440
[33]   Multiple infusions of CD20-targeted T cells and low-dose IL-2 after SCT for high-risk non-Hodgkin's lymphoma: A pilot study [J].
Lum, L. G. ;
Thakur, A. ;
Pray, C. ;
Kouttab, N. ;
Abedi, M. ;
Deol, A. ;
Colaiace, W. M. ;
Rathore, R. .
BONE MARROW TRANSPLANTATION, 2014, 49 (01) :73-79
[34]   In vivo accumulation of T cells in response to IL-2/anti-IL-2 mAb complexes is dependent in part on the TNF family ligand 4-1BBL [J].
Lin, Gloria H. Y. ;
Stone, John C. ;
Surh, Charles D. ;
Watts, Tania H. .
IMMUNOLOGY AND CELL BIOLOGY, 2012, 90 (07) :743-747
[35]   Low-dose cyclophosphamide combined with IL-2 inhibits tumor growth by decreasing regulatory T cells and increasing CD8+T cells and natural killer cells in mice [J].
Tang, Fei ;
Zhong, Qin ;
Yang, Zirong ;
Li, Hang ;
Pan, Cong ;
Huang, Limin ;
Ni, Tingting ;
Deng, Rong ;
Wang, Zi ;
Tan, Shisheng ;
Nie, Yingjie ;
Zhang, Yu .
IMMUNOBIOLOGY, 2022, 227 (03)
[36]   Protocol of the adaptive study of IL-2 dose frequency on regulatory T cells in type 1 diabetes (DILfrequency): a mechanistic, non-randomised, repeat dose, open-label, response-adaptive study [J].
Truman, Lucy A. ;
Pekalski, Marcin L. ;
Kareclas, Paula ;
Evangelou, Marina ;
Walker, Neil M. ;
Howlett, James ;
Mander, Adrian P. ;
Kennet, Jane ;
Wicker, Linda S. ;
Bond, Simon ;
Todd, John A. ;
Waldron-Lynch, Frank .
BMJ OPEN, 2015, 5 (12)
[37]   Tumor-infiltrating mast cells stimulate ICOS+ regulatory T cells through an IL-33 and IL-2 axis to promote gastric cancer progression [J].
Lv, Yipin ;
Tian, Wenqing ;
Teng, Yongsheng ;
Wang, Pan ;
Zhao, Yongliang ;
Li, Zhengyan ;
Tang, Shanhong ;
Chen, Weisan ;
Xie, Rui ;
Lu, Muhan ;
Zhuang, Yuan .
JOURNAL OF ADVANCED RESEARCH, 2024, 57 :149-162
[38]   Low-Dose IL-2 for In Vivo Expansion of CD4+ and CD8+ Regulatory T Cells in Nonhuman Primates [J].
Aoyama, A. ;
Klarin, D. ;
Yamada, Y. ;
Boskovic, S. ;
Nadazdin, O. ;
Kawai, K. ;
Schoenfeld, D. ;
Madsen, J. C. ;
Cosimi, A. B. ;
Benichou, G. ;
Kawai, T. .
AMERICAN JOURNAL OF TRANSPLANTATION, 2012, 12 (09) :2532-2537
[39]   In vivo manipulation of Vγ9Vδ2 T cells with zoledronate and low-dose interleukin-2 for immunotherapy of advanced breast cancer patients [J].
Meraviglia, S. ;
Eberl, M. ;
Vermijlen, D. ;
Todaro, M. ;
Buccheri, S. ;
Cicero, G. ;
La Mendola, C. ;
Guggino, G. ;
D'Asaro, M. ;
Orlando, V. ;
Scarpa, F. ;
Roberts, A. ;
Caccamo, N. ;
Stassi, G. ;
Dieli, F. ;
Hayday, A. C. .
CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 2010, 161 (02) :290-297
[40]   High-Dose IL-2 Induces Rapid Albumin Uptake by Endothelial Cells Through Src-Dependent Caveolae-Mediated Endocytosis [J].
Zloza, Andrew ;
Kim, Dae Won ;
Broucek, Joseph ;
Schenkel, Jason M. ;
Kaufman, Howard L. .
JOURNAL OF INTERFERON AND CYTOKINE RESEARCH, 2014, 34 (11) :915-919