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
相关论文
共 50 条
  • [1] IL-2 delivery by engineered mesenchymal stem cells re-invigorates CD8+ T cells to overcome immunotherapy resistance in cancer
    Bae, Joonbeom
    Liu, Longchao
    Moore, Casey
    Hsu, Eric
    Zhang, Anli
    Ren, Zhenhua
    Sun, Zhichen
    Wang, Xue
    Zhu, Jiankun
    Shen, Jiao
    Qiao, Jian
    Fu, Yang-Xin
    NATURE CELL BIOLOGY, 2022, 24 (12) : 1754 - 1765
  • [2] Characterization of cationic liposomes having IL-2 expressed on their external surface, and their affinity to cervical cancer cells expressing the IL-2 receptor
    Corona-Ortega, Teresa
    Rangel-Corona, Rosalva
    Hernandez-Jimenez, Miriam
    Baeza, Isabel
    Ibanez, Miguel
    Weiss-Steider, Benny
    JOURNAL OF DRUG TARGETING, 2009, 17 (07) : 496 - 501
  • [3] ALKS 4230: a novel engineered IL-2 fusion protein with an improved cellular selectivity profile for cancer immunotherapy
    Lopes, Jared E.
    Fisher, Jan L.
    Flick, Heather L.
    Wang, Chunhua
    Sun, Lei
    Ernstoff, Marc S.
    Alvarez, Juan C.
    Losey, Heather C.
    JOURNAL FOR IMMUNOTHERAPY OF CANCER, 2020, 8 (01)
  • [4] Selective targeting of engineered T cells using orthogonal IL-2 cytokine-receptor complexes
    Sockolosky, Jonathan T.
    Trotta, Eleonora
    Parisi, Giulia
    Picton, Lora
    Su, Leon L.
    Le, Alan C.
    Chhabra, Akanksha
    Silveria, Stephanie L.
    George, Benson M.
    King, Indigo C.
    Tiffany, Matthew R.
    Jude, Kevin
    Sibener, Leah V.
    Baker, David
    Shizuru, Judith A.
    Ribas, Antoni
    Bluestone, Jeffrey A.
    Garcia, K. Christopher
    SCIENCE, 2018, 359 (6379) : 1037 - +
  • [5] Engineered E. coli Nissle 1917 for delivery of bioactive IL-2 for cancer immunotherapy
    Tumas, Sarunas
    Meldgaard, Trine Sundebo
    Vaaben, Troels Holger
    Hernandez, Sara Suarez
    Rasmussen, Annemette Tengstedt
    Vazquez-Uribe, Ruben
    Hadrup, Sine Reker
    Sommer, Morten O. A.
    SCIENTIFIC REPORTS, 2023, 13 (01)
  • [6] Cancer immunotherapy with T-cell targeting cytokines: IL-2 and IL-7
    Kim, Ji-Hae
    Lee, Kun-Joo
    Lee, Seung-Woo
    BMB REPORTS, 2021, 54 (01) : 21 - 30
  • [7] An IL-2 mutein engineered to promote expansion of regulatory T cells arrests ongoing autoimmunity in mice
    Khoryati, Liliane
    Minh Nguyet Pham
    Sherve, McKenna
    Kumari, Swarnima
    Cook, Kevin
    Pearson, Josh
    Bogdani, Marika
    Campbell, Daniel J.
    Gavin, Marc A.
    SCIENCE IMMUNOLOGY, 2020, 5 (50)
  • [8] Evidence that cervical cancer cells secrete IL-2, which becomes an autocrine growth factor
    Rangel-Corona, R.
    Corona-Ortega, T.
    Soto-Cruz, I.
    Lopez-Labra, A.
    Pablo-Arcos, T.
    Torres-Guarneros, C. F.
    Weiss-Steider, B.
    CYTOKINE, 2010, 50 (03) : 273 - 277
  • [9] Dose-dependent enhancement of T-lymphocyte priming and CTL lysis following ionizing radiation in an engineered model of oral cancer
    Morisada, Megan
    Moore, Ellen C.
    Hodge, Rachel
    Friedman, Jay
    Cash, Harrison A.
    Hodge, James W.
    Mitchell, James B.
    Allen, Clint T.
    ORAL ONCOLOGY, 2017, 71 : 87 - 94
  • [10] IL-2 Induces Transient Arrest in the G1 Phase to Protect Cervical Cancer Cells from Entering Apoptosis
    del Carmen Lagunas-Cruz, Maria
    Valle-Mendiola, Arturo
    Trejo-Huerta, Jonathan
    Rocha-Zavaleta, Leticia
    de Lourdes Mora-Garcia, Maria
    Gutierrez-Hoya, Adriana
    Weiss-Steider, Benny
    Soto-Cruz, Isabel
    JOURNAL OF ONCOLOGY, 2019, 2019