CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Simulating the Evolution of Signaling Signatures During CART-Cell and Tumor Cell Interactions.
Simulating the Evolution of Signaling Signatures During CART-Cell and Tumor Cell Interactions.
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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。
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.
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