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工程化冷震荡癌细胞为黑色素瘤免疫疗法提供双重功能基因药物

Yali Liu^1,2, Changpeng Hu², Jingtao Huang¹

¹Chongqing Key Laboratory of Biomedical Analytics, Chongqing Science and Technology Commission, College of Pharmaceutical Sciences, Southwest University, Chongqing, 400715, China.

Advanced materials (Deerfield Beach, Fla.)

|November 26, 2025

概括

这项研究引入了一种通过工程瘤细胞传递的新型双功能等离子体,以增强黑色素瘤免疫疗法. 该系统增强了T细胞透和抗瘤作用,为固体瘤提供了有前途的基因疗法.

科学领域:

在瘤学瘤学.
基因治疗基因治疗
免疫学免疫学免疫学

背景情况:

黑色素瘤免疫疗法面临着诸如抵抗免疫检查点封锁和T细胞透到瘤微环境 (TME) 的挑战.
PCSK9被确定为一种免疫抑制因子,影响CD8+ T细胞活性.
CXCL9是一种化学激素,已知可以将T细胞招募到瘤部位.

研究的目的:

开发一种新的双功能基因疗法系统,以克服黑色素瘤免疫疗法的局限性.
将PCSK9淘汰的腺基编辑与CXCL9过度表达相结合,以增强T细胞的招募和活性.
利用工程液处理 (LNT) 瘤细胞作为治疗等离子体的"特洛伊木马"输送系统.

主要方法:

一种双重功能等离子体 (CXCL9-ABE_PCSK9) 设计用于PCSK9的淘汰和CXCL9的过度表达.
该等离子体被封装在脂质体中,并加载到LNT瘤细胞上,形成LNT@LipoC9AP粒子.
用RGD4C (R-LNT@LipoC9AP) 进一步设计了LNT@LipoC9AP颗粒,以增强向黑色素瘤中的αvβ3整合素.

主要成果:

LNT@LipoC9AP颗粒有效地增加了CD8+T细胞的透,并在体外和体内表现出强大的抗瘤作用.
与非工程颗粒相比,R-LNT@LipoC9AP显示出优越的瘤积累和增强的治疗疗效.
设计的基于LNT细胞的系统表现出了有利的安全性.

结论:

基于LNT细胞的CXCL9和ABE联合递送系统_PCSK9有效地克服了目前瘤免疫治疗的局限性.
这种新型基因治疗策略在治疗固体瘤,特别是黑色素瘤方面表现有前途.
双功能的方法增强了T细胞透和抗瘤活性,这代表了癌症治疗的重大进展.

关键词:

具有双重功能的基因医学工程化瘤细胞载体的人造细胞基因编辑基因编辑黑色素瘤免疫疗法免疫疗法瘤微环境是一个微环境.

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