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当地的mRNA编码细胞因子尾酒给予强大的抗瘤免疫力

Zhigang Li¹, Ling Hu¹, Yi Wang¹

¹Department of Research and Development, Liverna Therapeutics Inc., Zhuhai, China.

Frontiers in immunology

|September 18, 2024

概括

用脂质纳米粒子封装的mRNA编码细胞因子 (IL-12,IL-7,IFN-α) 的局部免疫疗法有效治疗瘤并增强抗瘤免疫力,克服全身细胞因子治疗的局限性.

科学领域:

生物技术是生物技术.
免疫学免疫学免疫学
在瘤学瘤学.

背景情况:

使用炎症性细胞因子 (如INTERLEUKIN (IL) - 2和INTERFERON (IFN) -α) 的系统性免疫疗法在癌症治疗中已获得临床验证.
系统性细胞因子治疗的局限性包括蛋白质半衰期短和剂量限制性毒性.

研究的目的:

通过使用编码细胞因子尾酒 (IL-12,IL-7,IFN-α) 的脂质纳米粒子 (LNP) 封装的mRNA研究局部免疫疗法的疗效.
评估这种方法在克服全身治疗局限性和增强抗瘤免疫力方面的潜力.

主要方法:

内注射LNP封装的mRNA尾酒编码IL-12,IL-7和IFN-α在同基因小鼠模型中.
评估瘤回归,抗瘤免疫记忆和瘤微环境炎症.
在人性化小鼠模型中评估与免疫检查点阻塞的联合治疗和人类细胞因子mRNA的疗效.

主要成果:

细胞因子mRNA尾酒在多个小鼠模型中诱导了显著的瘤回归.
在一个合成基因模型中观察到抗瘤免疫记忆.
免疫检查点封锁增强了细胞因子mRNAs的抗瘤疗效.
人类细胞因子mRNA在人性化模型中表现出强大的抗瘤疗效.
从机制上讲,细胞因子mRNAs促进了瘤微环境的炎症,增加了T细胞透和细胞因子/化学因子的产生.

结论:

用LNP封装的细胞因子mRNAs进行局部免疫疗法为癌症治疗提供了一个有前途的策略.
这种方法克服了系统治疗的局限性,并有效调节瘤免疫微环境.
与免疫检查点抑制剂相结合,可以进一步改善治疗结果.

关键词:

癌症免疫疗法免疫疗法细胞因子细胞因子介质蛋白-12 介质蛋白-12 的作用.内注射口服的使用方法它们是mRNARNA.

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