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辐射工程瘤细胞衍生微粒重塑瘤免疫微环境并增强抗瘤免疫力

Yan Hu¹, Yajie Sun¹, Zhiyun Liao¹

¹Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Institute of Radiation Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

Molecular therapy : the journal of the American Society of Gene Therapy

|December 15, 2023

概括

工程微粒模仿放射治疗 (RT) 激活抗瘤免疫力. 这种新的方法,使用辐射瘤细胞释放的微粒 (RT-MPs),显示出治疗晚期癌症和建立长期免疫记忆的希望.

科学领域:

在瘤学瘤学.
免疫治疗是一种免疫疗法.
生物技术是生物技术.

背景情况:

放射治疗 (RT) 是癌症治疗的基石,但它的应用有限.
辐射诱导的旁观者效应 (RIBE) 涉及辐射暴露后的细胞间通信.
来自瘤细胞的微粒子可以调解细胞间信号和免疫反应.

研究的目的:

开发一种模仿RT的替代癌症治疗方法,使用微粒介质.
设计微粒来增强抗瘤免疫激活,用于晚期癌症治疗.
评估单独和与免疫治疗结合的工程微粒的治疗疗效.

主要方法:

辐射瘤细胞释放的微粒 (RT-MPs) 用特定的细胞因子/化学因子产生和设计.
进行了体外和体内研究,以评估免疫激活和抗瘤作用.
治疗疗效被评估在恶性流 (MPE) 的小鼠模型中,包括与PD-1单克隆抗体 (mAb) 的联合治疗.

主要成果:

工程RT-MPs,特别是tIL-15/tCCL19-RT-MPs,有效地激活了抗瘤免疫反应.
用tIL-15/tCCL19-RT-MPs治疗显著改善了MPE小鼠的生存率,在某些情况下达到完全缓解.
与tIL-15/tCCL19-RT-MPs和PD-1 mAb的联合治疗通过激活CD8+T细胞和巨细胞,诱导瘤生长抑制和免疫记忆,导致60%的治愈率.

结论:

工程RT-MPs代表了对癌症的有希望的替代策略,这些癌症对传统RT无反应.
这种方法利用RIBE诱导强大的抗瘤免疫力并建立持久记忆.
使用工程RT-MP和检查点抑制剂进行组合疗法为癌症缓解提供了潜在的途径,即使在晚期.

关键词:

细胞因子细胞因子细胞外囊泡中的细胞外囊泡.免疫疗法免疫疗法被照射的瘤细胞释放的微粒.恶性多叶流血恶性多叶流血辐射疗法辐射疗法

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