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一个自我激活的IL-15化学细胞因子受体,以加强癌症免疫疗法

Sumei Chen¹, Lingrong Yang², Bing Xia³

¹Department of Radiation Oncology, Hangzhou Cancer Hospital, Hangzhou, Zhejiang, 310002, People's Republic of China.

ImmunoTargets and therapy

|October 15, 2024

概括

与其IL2Rβ受体连接Interleukin-15 (IL-15) 增强了自然杀手 (NK) 细胞的抗瘤活性,并防止了全身毒性. 这种新的平台使NK细胞能够改善癌症免疫治疗,而不会产生不良影响.

科学领域:

免疫学免疫学免疫学
细胞生物学细胞生物学
生物技术是生物技术.

背景情况:

持续的细胞因子信号传递对NK细胞抗瘤活性至关重要.
介素-15 (IL-15) 对于CAR-NK和CAR-T细胞免疫疗法至关重要.
目前的IL-15策略存在系统性毒性,瘤发生和自身免疫性疾病的风险.

研究的目的:

开发一种用于增强IL-15疗效的新平台.
为了减轻与IL-15免疫疗法相关的全身毒性.
为了改善NK细胞介导的抗瘤反应.

主要方法:

开发了一个平台 (IL15RB),将IL-15与其受体IL2Rβ结合起来.
工程 NK92 细胞表达 IL15RB (NK92^IL15RB).
评估NK92^IL15RB扩张,抗癌活性,细胞因子信号传递和对其他药物的反应.

主要成果:

NK92^IL15RB细胞在没有外源细胞因子的情况下无限期扩大,并显示出优异的抗癌活性.
NK92^IL15RB表现出对辐射和IL-4的抗性,但TGFβ1.1的杀死性降低.
IL15RB诱导了STAT3激活,慢性暴露导致疲劳;CAR-CD19和抗PD1组合增强了活性.

结论:

将IL-15与IL2Rβ结合,增强了NK细胞的细胞分解活性.
这种绑定策略可以防止与IL-15相关的全身毒性风险.
IL15RB平台为晚期癌症免疫疗法提供了一个有前途的方法.

关键词:

在IL-15中,IL-15是最常见的.在 IL15RBB 中.这种IL2RB受体是IL2RB受体.癌症免疫疗法免疫疗法自然杀手细胞是自然杀手细胞.

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