文献检索文档翻译深度研究
Suppr Zotero 插件Zotero 插件
邀请有礼套餐&价格历史记录

新学期,新优惠

限时优惠:9月1日-9月22日

30天高级会员仅需29元

1天体验卡首发特惠仅需5.99元

了解详情
不再提醒
插件&应用
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
高级版
套餐订阅购买积分包
AI 工具
文献检索文档翻译深度研究
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利:CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2025

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

作者信息

Barros Luciana R C, Paixão Emanuelle A, Valli Andrea M P, Naozuka Gustavo T, Fassoni Artur C, Almeida Regina C

机构信息

Center for Translational Research in Oncology, Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas da Faculdade de Medicina ds Universidade de São Paulo, São Paulo 01246-000, Brazil.

Graduate Program, Laboratório Nacional de Computação Científica, Petrópolis 25651-075, Brazil.

出版信息

Cancers (Basel). 2021 Jun 11;13(12):2941. doi: 10.3390/cancers13122941.


DOI:10.3390/cancers13122941
PMID:34208323
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8231202/
Abstract

Immunotherapy has gained great momentum with chimeric antigen receptor T cell (CAR-T) therapy, in which patient's T lymphocytes are genetically manipulated to recognize tumor-specific antigens, increasing tumor elimination efficiency. In recent years, CAR-T cell immunotherapy for hematological malignancies achieved a great response rate in patients and is a very promising therapy for several other malignancies. Each new CAR design requires a preclinical proof-of-concept experiment using immunodeficient mouse models. The absence of a functional immune system in these mice makes them simple and suitable for use as mathematical models. In this work, we develop a three-population mathematical model to describe tumor response to CAR-T cell immunotherapy in immunodeficient mouse models, encompassing interactions between a non-solid tumor and CAR-T cells (effector and long-term memory). We account for several phenomena, such as tumor-induced immunosuppression, memory pool formation, and conversion of memory into effector CAR-T cells in the presence of new tumor cells. Individual donor and tumor specificities are considered uncertainties in the model parameters. Our model is able to reproduce several CAR-T cell immunotherapy scenarios, with different CAR receptors and tumor targets reported in the literature. We found that therapy effectiveness mostly depends on specific parameters such as the differentiation of effector to memory CAR-T cells, CAR-T cytotoxic capacity, tumor growth rate, and tumor-induced immunosuppression. In summary, our model can contribute to reducing and optimizing the number of in vivo experiments with in silico tests to select specific scenarios that could be tested in experimental research. Such an in silico laboratory is an easy-to-run open-source simulator, built on a Shiny R-based platform called CART. It contains the results of this manuscript as examples and documentation. The developed model together with the CART platform have potential use in assessing different CAR-T cell immunotherapy protocols and its associated efficacy, becoming an accessory for in silico trials.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/309c/8231202/012423943de4/cancers-13-02941-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/309c/8231202/b9e9af630bda/cancers-13-02941-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/309c/8231202/ad790c85e9af/cancers-13-02941-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/309c/8231202/9781d22ffb8d/cancers-13-02941-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/309c/8231202/fe94b893eaf1/cancers-13-02941-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/309c/8231202/ec1b70c03bd4/cancers-13-02941-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/309c/8231202/1bc497ce5e1f/cancers-13-02941-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/309c/8231202/012423943de4/cancers-13-02941-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/309c/8231202/b9e9af630bda/cancers-13-02941-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/309c/8231202/ad790c85e9af/cancers-13-02941-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/309c/8231202/9781d22ffb8d/cancers-13-02941-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/309c/8231202/fe94b893eaf1/cancers-13-02941-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/309c/8231202/ec1b70c03bd4/cancers-13-02941-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/309c/8231202/1bc497ce5e1f/cancers-13-02941-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/309c/8231202/012423943de4/cancers-13-02941-g007.jpg

相似文献

[1]
CART-A Mathematical Model of CAR-T Immunotherapy in Preclinical Studies of Hematological Cancers.

Cancers (Basel). 2021-6-11

[2]
Chimeric antigen receptor T cells engineered to recognize the P329G-mutated Fc part of effector-silenced tumor antigen-targeting human IgG1 antibodies enable modular targeting of solid tumors.

J Immunother Cancer. 2022-7

[3]
Mucosal-associated invariant T (MAIT) cells, a new source of universal immune cells for chimeric antigen receptor (CAR)-cell therapy.

Bull Cancer. 2021-10

[4]
Modeling Patient-Specific CAR-T Cell Dynamics: Multiphasic Kinetics via Phenotypic Differentiation.

Cancers (Basel). 2022-11-14

[5]
Any closer to successful therapy of multiple myeloma? CAR-T cell is a good reason for optimism.

Stem Cell Res Ther. 2021-3-29

[6]
The Role of Immunological Synapse in Predicting the Efficacy of Chimeric Antigen Receptor (CAR) Immunotherapy.

Cell Commun Signal. 2020-8-25

[7]
Off-the-shelf Vδ1 gamma delta T cells engineered with glypican-3 (GPC-3)-specific chimeric antigen receptor (CAR) and soluble IL-15 display robust antitumor efficacy against hepatocellular carcinoma.

J Immunother Cancer. 2021-12

[8]
First immunotherapeutic CAR-T cells against the immune checkpoint protein HLA-G.

J Immunother Cancer. 2021-3

[9]
CAR-engineered NK cells; a promising therapeutic option for treatment of hematological malignancies.

Stem Cell Res Ther. 2021-7-2

[10]
Chimeric antigen receptor-engineered T-cell therapy for liver cancer.

Hepatobiliary Pancreat Dis Int. 2018-5-24

引用本文的文献

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

Front Immunol. 2025-8-1

[2]
Design specifications for biomedical virtual twins in engineered adoptive cellular immunotherapies.

NPJ Digit Med. 2025-8-1

[3]
Modernizing Preclinical Drug Development: The Role of New Approach Methodologies.

ACS Pharmacol Transl Sci. 2025-5-29

[4]
Spatiotemporal dynamics of tumor-CAR T-cell interaction following local administration in solid cancers.

PLoS Comput Biol. 2025-6-3

[5]
Tumor Growth, Proliferation and Diffusion in Osteosarcoma.

Acta Biotheor. 2025-3-18

[6]
Computational modelling of CAR T-cell therapy: from cellular kinetics to patient-level predictions.

EBioMedicine. 2025-3

[7]
Mathematical Model of CAR T-Cell Therapy for a B-Cell Lymphoma Lymph Node.

Bull Math Biol. 2025-2-7

[8]
A framework integrating multiscale in-silico modeling and experimental data predicts CD33CAR-NK cytotoxicity across target cell types.

bioRxiv. 2025-1-2

[9]
Rapidly Manufactured CAR-T with Conserved Cell Stemness and Distinctive Cytokine-Secreting Profile Shows Improved Anti-Tumor Efficacy.

Vaccines (Basel). 2024-11-28

[10]
Finding potential targets in cell-based immunotherapy for handling the challenges of acute myeloid leukemia.

Front Immunol. 2024

本文引用的文献

[1]
Relapse and Resistance to CAR-T Cells and Blinatumomab in Hematologic Malignancies.

Clin Hematol Int. 2019-6-11

[2]
In Search of an Ideal CAR-T Cell Antigen Target.

Crit Rev Immunol. 2021

[3]
Dual-Target CAR-Ts with On- and Off-Tumour Activity May Override Immune Suppression in Solid Cancers: A Mathematical Proof of Concept.

Cancers (Basel). 2021-2-9

[4]
Counteracting CAR T cell dysfunction.

Oncogene. 2021-1

[5]
Development of CAR-T cell therapy for B-ALL using a point-of-care approach.

Oncoimmunology. 2020

[6]
Conducting a Virtual Clinical Trial in HER2-Negative Breast Cancer Using a Quantitative Systems Pharmacology Model With an Epigenetic Modulator and Immune Checkpoint Inhibitors.

Front Bioeng Biotechnol. 2020-2-25

[7]
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

[8]
Mathematical deconvolution of CAR T-cell proliferation and exhaustion from real-time killing assay data.

J R Soc Interface. 2020-1

[9]
Mechanisms of Relapse After CD19 CAR T-Cell Therapy for Acute Lymphoblastic Leukemia and Its Prevention and Treatment Strategies.

Front Immunol. 2019-11-12

[10]
Determinants of combination GM-CSF immunotherapy and oncolytic virotherapy success identified through in silico treatment personalization.

PLoS Comput Biol. 2019-11-27

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

推荐工具

医学文档翻译智能文献检索