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Tumor Immunotherapy

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.

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使用基于NKG2D的适配器CAR T细胞进行固体瘤免疫疗法.

Jana Obajdin¹, Daniel Larcombe-Young¹, Maya Glover²

¹King's College London, School of Cancer and Pharmaceutical Sciences, CAR Mechanics Lab, London SE1 9RT, UK.

Cell reports. Medicine

|November 20, 2024

概括

此摘要是机器生成的。

针对NKG2D配体 (NKG2DLs) 的工程T细胞显示出强大的抗瘤活性. 新的NKG2D/Dap10-12仿真抗原受体 (CAR) 疗法消除了瘤,并改善了模型中的生存率.

关键词:

在Dap10中使用Dap10 在Dap12中使用Dap12.在NKG2D中,它是NKG2D.适配器适配器适配器适配器仿制性抗原受体的仿制性抗原受体

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科学领域:

免疫学免疫学免疫学
癌症生物学癌症生物学
细胞疗法细胞疗法

背景情况:

NKG2D配体 (NKG2DLs) 在癌细胞上得到广泛表达,具有治疗点.
现有的仿真抗原受体 (CAR) 策略在向NKG2DL表达瘤方面存在局限性.

研究的目的:

开发和评估一种名为NKG2D/Dap10-12的新型适应器CAR,用于向癌细胞上的NKG2DL.
在临床前癌症模型中评估NKG2D/Dap10-12CAR T细胞的疗效和潜在机制.

主要方法:

工程T细胞与Dap10和Dap12内域 (NKG2D/Dap10-12 CAR) 组成的融合蛋白共同表达NKG2D.
在具有NKG2DL表达瘤的已建立异种移植模型中评估治疗疗效.
在一组CAR中进行结构功能分析,以确定效力的关键决定因素.
分析工程T细胞的细胞代谢和转录组学.

主要成果:

在多个异种移植模型中,NKG2D/Dap10-12 T 细胞显示出令人信服的疗效,根除或控制瘤.
实现了持久的反应,长期存活和拒绝瘤再挑战.
疗效明显超过了临床阶段NKG2D-CD3ζ CAR. 的疗效.
功效与信号单位的接近,NKG2D表达,适应器结构,外源Dap10和ITIM号码有关.

结论:

NKG2D/Dap10-12 CAR代表了针对NKG2DL表达性癌症的强有力的新策略.
优化的CAR设计,包括适配器结构和信号图案,对于治疗疗效至关重要.
NKG2D/Dap10-12 CAR T 细胞表现出增强的代谢适应性和重新编程的转录以改善抗瘤功能.