细胞表面绑定核酸治疗方案 强大的和瘤响应增强收养细胞治疗的强化
Mengqian Gao1,2, Yingyu Liu3,4, Lei Zhao1,2
1The Fourth Affiliated Hospital of Soochow University, College of Pharmaceutical Sciences, Suzhou Medical College of Soochow University, Soochow University, Suzhou, 215123, P. R. China.
Advanced materials (Deerfield Beach, Fla.)
|May 3, 2025
概括
核酸治疗药物 (NAT) 通过阻断固体瘤中的免疫抑制性腺和PD-1/PD-L1通路来增强采用性T细胞疗法 (ACT). 这种双重阻断显著提高T细胞透和有效性,即使在冷瘤中.
科学领域:
- 免疫学 免疫学 免疫学
- 生物技术是生物技术.
- 癌症治疗 癌症治疗
背景情况:
- 采用T细胞疗法 (ACT) 对固体瘤的疗效受到免疫抑制瘤微环境 (TME) 的阻碍.
- 系统性免疫刺激剂通常会导致毒性,并且对TME内的ACT细胞提供不够的支持.
研究的目的:
- 开发细胞表面固的核酸疗法 (NAT),通过同时向免疫抑制性腺和PD-1/PD-L1通路来增强ACT.
- 提高ACT在固体瘤的疗效,包括免疫学上"冷"的瘤.
主要方法:
- 针对PD-L1 (aptPD-L1) 和ATP (aptATP) 的双重作用DNA吸收体 (aptDual) 进行细胞表面定.
- 在体内,aptDual与ACT细胞的同位定位以透TME.
- 在ATP结合后对aptPD-L1的响应释放,加上aptATP对ATP和腺的清理,以破坏腺轴.
主要成果:
- NAT背包显示了与TME中的ACT细胞的时空共定位.
- 腺和PD-1/PD-L1通路的双重抑制导致功能瘤透ACT细胞增加40倍.
- 在多种固体瘤模型中增强TCR-T和CAR-T细胞的疗效,包括冷瘤.
结论:
- 细胞表面固的NAT提供了一种多功能且安全的策略,以增强ACT对固体瘤的疗效.
- 在TME内的免疫抑制途径的协同阻塞是增强采用T细胞疗法的有效方法.
- 这种NAT背包系统提供了一种简单的方法来改善T细胞介导癌症免疫疗法.
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