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模拟 CAR-T 细胞与肿瘤细胞相互作用过程中信号特征的演化

英文原题:Simulating the Evolution of Signaling Signatures During CART-Cell and Tumor Cell Interactions.

查看英文原题

Simulating the Evolution of Signaling Signatures During CART-Cell and Tumor Cell Interactions.

PubMed 2023/07/01(内容时间) Annu Int Conf IEEE Eng Med Biol Soc

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中文摘要

免疫疗法已被证明在癌症治疗中具有显著的治疗效果。过去十年中,过继性细胞疗法,如CAR-T 细胞(CAR-T 细胞)疗法,已获得FDA批准用于治疗特定癌症。此外,还有许多正在进行的临床试验在研究更多的设计和靶点。然而,尽管CAR-T 细胞疗法令人兴奋且具有广阔前景,但不同研究、患者和癌症之间的治疗缓解率差异很大。仍有一个未满足的需求,即开发能够更准确预测CAR-T 细胞功能和临床疗效的计算框架。在此,我们提出了一种用逻辑规则模拟的粗粒度模型,该模型展示了CAR-T 细胞与肿瘤细胞相互作用后信号特征的演变,并允许在实验前基于计算机预测CAR-T 细胞功能。临床相关性——分析CAR-T 细胞信号特征可为未来CAR受体设计和旨在改善治疗应答的联合治疗方法提供信息。

展开英文摘要原文

Immunotherapies have been proven to have significant therapeutic efficacy in the treatment of cancer. The last decade has seen adoptive cell therapies, such as chimeric antigen receptor T-cell (CART-cell) therapy, gain FDA approval against specific cancers.

Additionally, there are numerous clinical trials ongoing investigating additional designs and targets. Nevertheless, despite the excitement and promising potential of CART-cell therapy, response rates to therapy vary greatly between studies, patients, and cancers. There remains an unmet need to develop computational frameworks that more accurately predict CART-cell function and clinical efficacy.

Here we present a coarse-grained model simulated with logical rules that demonstrates the evolution of signaling signatures following the interaction between CART-cells and tumor cells and allows for in silico based prediction of CART-cell functionality prior to experimentation. Clinical Relevance- Analysis of CART-cell signaling signatures can inform future CAR receptor design and combination therapy approaches aimed at improving therapy response.

论文信息

作者
Shah V、Womack J、Zamora AE、Terhune SS、Dash RK
文献类型
美国 NIH 资助研究
期刊
Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference2023 Jul
原文标识
PubMed 38083755 · DOI 10.1109/EMBC40787.2023.10340076