利用向光动力疗法协同激活多发性髓瘤中T细胞和NK细胞反应
Zhaoyun Liu1, Xiaohan Liu1, Jingyi Ma2
1Department of Hematology, Tianjin Medical University General Hospital, Tianjin Key Laboratory of Bone Marrow Failure and Malignant Hemopoietic Clone Control, Tianjin Institute of Hematology, State Key Laboratory of Experimental Hematology, Tianjin, 300052, China.
Advanced materials (Deerfield Beach, Fla.)
|November 29, 2025
概括
这项研究引入了一种新的光动力疗法 (PDT) 平台,可以同时激活T细胞和自然杀手细胞. 这种双方向的方法可以增强治疗多发性骨髓瘤 (MM) 的抗瘤免疫力.
科学领域:
- 免疫学 免疫学 免疫学
- 材料科学 材料科学 材料科学
- 在瘤学瘤学.
背景情况:
- 多发性骨髓瘤 (MM) 是一种无法治愈的血液癌症,其特点是骨髓微环境中的免疫抑制.
- 恢复适应性和先天性免疫力是MM的关键治疗策略.
- 现有的疗法在克服MM的免疫逃避方面面临挑战.
研究的目的:
- 开发一种新的光动力疗法 (PDT) 平台,以协同激活针对多发性骨髓瘤 (MM) 的适应性和先天性免疫力.
- 设计和合成基于聚合诱导排放光原体 (AIEgen) 的高性能光敏剂,用于向的MM治疗.
- 在临床前MM模型中评估开发的免疫治疗策略的体内疗效.
主要方法:
- 基于AIEgen的光敏感剂的合成和表征,具有双受体分子设计.
- 将AIEgen配制成纳米粒子,并与B细胞成熟抗原 (BCMA) 抗体功能化,用于向传递.
- 在体外和体内评估纳米剂通过NKG2D/MICA/B相互作用诱导免疫细胞死亡,树突细胞激活,T细胞原始化和NK细胞激活的能力.
- 在NSG小鼠模型中评估抗瘤效应,该模型植入患者衍生MM细胞.
主要成果:
- 一种新型的双受体AIEgen表现出卓越的PDT疗效,并被制成向纳米颗粒.
- 该纳米剂成功触发了免疫细胞死亡,树突细胞激活和T细胞在光激活后启动.
- 通过ATM/SMAD1通路对MM细胞中MICA/B表达的升级导致通过NKG2D参与增强NK细胞激活.
- 在体内研究显示,患者衍生的T细胞和NK细胞的强烈激活,导致显著的抗MM效应.
结论:
- 开发的PDT平台提供了一种双方向的免疫治疗策略,以克服多发性骨髓瘤的免疫抑制.
- 这种方法协同利用适应性 (T细胞) 和先天性 (NK细胞) 免疫力,增强抗癌免疫疗法.
- 这种新的策略有望改善多发性骨髓瘤患者的治疗结果.
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