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少即是多:使用数学指导方法减少小鼠模型中给予的嵌合抗原受体 T 细胞数量。

Less is more: reducing the number of administered chimeric antigen receptor T cells in a mouse model using a mathematically guided approach.

机构信息

Tel Aviv Sourasky Medical Center, 6 Weizmann St., 6423906, Tel Aviv, Israel.

Weizmann Institute of Science, Rehovot, Israel.

出版信息

Cancer Immunol Immunother. 2020 Jul;69(7):1165-1175. doi: 10.1007/s00262-020-02516-9. Epub 2020 Mar 4.


DOI:10.1007/s00262-020-02516-9
PMID:32130452
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11027665/
Abstract

Chimeric antigen receptor T cell (CAR-T) therapy is a novel approved treatment for hematological malignancies, still under development for solid tumors. Here, we use a rate equation-based mathematical model to discover regimens and schedules that maintain efficacy while potentially reducing toxicity by decreasing the amount of CAR-T infused. Tested on an in vivo murine model of spontaneous breast cancer, we show that our mathematical model accurately recapitulates in vivo tumor growth results achieved in the previous experiments. Moreover, we use the mathematical model to predict results of new therapy schedules and successfully prospectively validated these predictions in the in vivo. We conclude that using one tenth and even one percent of a full CAR-T dose used in preclinical trials can achieve efficacious results similar to full dose treatment.

摘要

嵌合抗原受体 T 细胞(CAR-T)疗法是一种新型的血液恶性肿瘤治疗方法,目前正在开发用于实体瘤。在这里,我们使用基于速率方程的数学模型来发现方案和时间表,通过减少输注的 CAR-T 量来保持疗效,同时降低毒性。在自发性乳腺癌的体内小鼠模型上进行测试,我们表明我们的数学模型准确地再现了以前实验中体内肿瘤生长结果。此外,我们使用数学模型预测新治疗方案的结果,并成功地在体内前瞻性验证了这些预测。我们得出结论,使用临床前试验中全剂量 CAR-T 的十分之一甚至百分之一可以达到与全剂量治疗相似的有效结果。

相似文献

[1]
Less is more: reducing the number of administered chimeric antigen receptor T cells in a mouse model using a mathematically guided approach.

Cancer Immunol Immunother. 2020-3-4

[2]
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[3]
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[4]
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[5]
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[6]
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[7]
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[8]
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[9]
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[10]
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引用本文的文献

[1]
Mathematical models and computational approaches in CAR-T therapeutics.

Front Immunol. 2025-8-1

[2]
In silico study of heterogeneous tumour-derived organoid response to CAR T-cell therapy.

Sci Rep. 2024-5-29

[3]
A systems and computational biology perspective on advancing CAR therapy.

Semin Cancer Biol. 2023-9

[4]
Engineering T-cells with chimeric antigen receptors to combat hematological cancers: an update on clinical trials.

Cancer Immunol Immunother. 2022-10

[5]
Clinical Pharmacology Perspectives for Adoptive Cell Therapies in Oncology.

Clin Pharmacol Ther. 2022-11

[6]
CART-A Mathematical Model of CAR-T Immunotherapy in Preclinical Studies of Hematological Cancers.

Cancers (Basel). 2021-6-11

[7]
CAR T cells: Building on the CD19 paradigm.

Eur J Immunol. 2021-9

[8]
CAR-T cells: Early successes in blood cancer and challenges in solid tumors.

Acta Pharm Sin B. 2021-5

本文引用的文献

[1]
The Dark Side of IFN-γ: Its Role in Promoting Cancer Immunoevasion.

Int J Mol Sci. 2017-12-28

[2]
Long-Duration Complete Remissions of Diffuse Large B Cell Lymphoma after Anti-CD19 Chimeric Antigen Receptor T Cell Therapy.

Mol Ther. 2017-7-13

[3]
Engineering Chimeric Antigen Receptor T-Cells for Racing in Solid Tumors: Don't Forget the Fuel.

Front Immunol. 2017-4-3

[4]
Lymphoma Remissions Caused by Anti-CD19 Chimeric Antigen Receptor T Cells Are Associated With High Serum Interleukin-15 Levels.

J Clin Oncol. 2017-6-1

[5]
Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy.

Cell. 2017-2-9

[6]
Dual-specific Chimeric Antigen Receptor T Cells and an Indirect Vaccine Eradicate a Variety of Large Solid Tumors in an Immunocompetent, Self-antigen Setting.

Clin Cancer Res. 2017-5-15

[7]
Clinical manufacturing of CAR T cells: foundation of a promising therapy.

Mol Ther Oncolytics. 2016-6-15

[8]
Improving Bacillus Calmette-Guérin (BCG) immunotherapy for bladder cancer by adding interleukin 2 (IL-2): a mathematical model.

Math Med Biol. 2016-6

[9]
Elimination of progressive mammary cancer by repeated administrations of chimeric antigen receptor-modified T cells.

Mol Ther. 2014-5

[10]
Infusion of donor-derived CD19-redirected virus-specific T cells for B-cell malignancies relapsed after allogeneic stem cell transplant: a phase 1 study.

Blood. 2013-9-12

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