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从妇科癌症中有效扩张瘤透淋巴细胞

Tetsuya Matsukawa^1,2, Tsunenori Ouchida¹, Taeko Hayakawa¹

¹Division of Tumor Immunology, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan.

Journal of immunology (Baltimore, Md. : 1950)

|September 26, 2025

概括

用抗CD3抗体和CD28联合刺激直接刺激瘤透淋巴细胞 (TILs),可增强其扩张和瘤对妇科癌症的反应性. 这种方法提高了采用免疫治疗的潜力.

科学领域:

免疫学免疫学免疫学
在瘤学瘤学.
细胞疗法细胞疗法

背景情况:

使用瘤透淋巴细胞 (TILs) 的采用免疫疗法对固体瘤,包括妇科恶性瘤,显示出前景.
目前的TIL扩展协议,通常使用高剂量的IL-2 (HD-IL2),可能不适合所有癌症类型.

研究的目的:

研究有效的方法来扩大从妇科癌症患者的TILs.
为了比较HD-IL2的疗效与用于TIL扩张的新兴刺激方法.

主要方法:

用HD-IL2培养TIL或用表达抗CD3mAb和CD80 (αCD3/CD80) 的K562细胞刺激TIL.
评估了TIL增殖,表型 (PD-1,CD28表达) 和瘤反应性 (IFN-γ分泌,CD107a表达).
评估了DUSP4在TIL增殖中的作用和基因工程对仿真细胞因子受体的影响.

主要成果:

与HD-IL2-TIL相比,αCD3/CD80刺激的TIL的扩散率显著增加.
扩展的TIL群体表达了高水平的PD-1和CD28,CD28协同刺激对于克服PD-1介导的生长抑制至关重要.
通过ERK酸化,DUSP4被确定为TIL增殖的负调节者.
αCD3/CD80-TILs表现出瘤反应性,并被有效地设计为在小鼠模型中增强体内持久性和抗瘤作用.

结论:

使用抗CD3 mAb和CD28联合刺激的直接刺激提供了一种有效的方法,用于扩大从妇科癌症中瘤反应性TILs.
对TILs进行基因改造以改变细胞因子信号传递,这为增强它们的功能提供了一种策略,并可能取代输注后的细胞因子管理.

关键词:

CD28 CD28 CD28 CD28 CD28 CD28 CD28 CD28 CD28 CD28 CD28 CD28 CD28 CD28 CD28 CD28 CD28 CD28 在TIL TIL.收养免疫疗法采用免疫疗法.细胞因子细胞因子妇科癌症妇科癌症

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