针对瘤免疫治疗的OX40联体的非病毒媒介基因转移

针对瘤免疫治疗的OX40联体的非病毒媒介基因转移

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Updated: Jun 21, 2025

Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo

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Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo

Published on: January 7, 2019

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Olga A Rakitina¹, Alexey I Kuzmich¹, Olga A Bezborodova¹

¹Group of Gene Immuno-Oncotherapy, Department of Genomics and Postgenomic Technologies, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, Moscow, Russia.

Frontiers in immunology

|July 15, 2024

概括

这项研究开发了一种使用OX40L/PPT纳米颗粒用于局部癌症治疗的新型非病毒基因疗法. 该疗法在与免疫检查点阻塞 (ICB) 结合时,显示出显著的抗瘤效应和改善结果.

科学领域:

在瘤学瘤学.
免疫治疗是一种免疫疗法.
基因治疗基因治疗

背景情况:

免疫检查点阻塞 (ICB) 是一种标准的癌症治疗方法,但反应率有限.
系统性免疫疗法会引起不良反应;需要局部治疗.
非病毒基因免疫疗法为癌症治疗提供了长时间的局部基因表达.

研究的目的:

评估一种非病毒基因免疫疗法的疗效,该疗法将PEG-PEI-TAT共聚合物 (PPT) 与OX40L编码的等离子体DNA结合起来.
评估内OX40L/PPT纳米颗粒的局部抗瘤作用和安全性.
为了研究OX40L/PPT与PD-1免疫检查点阻塞的联合治疗.

主要方法:

使用凝流动性,动态光散射和体外转染试验对OX40L/PPT纳米粒子进行表征.
在内服药后,对CT26,B16F0和4T1瘤模型的抗瘤疗效的评估.
对免疫细胞群和与免疫相关的不良事件 (irAEs) 的分析.

主要成果:

在癌症模型中,OX40L/PPT纳米粒子在体外促进了OX40L蛋白的表达.
在CT26和B16F0模型中,内OX40L/PPT抑制了瘤生长,在4T1.1中出现了趋势.
治疗增加了有效的NK和T杀手细胞,减少了髓状细胞,并且没有显示出irrAEs.
与PD-1 ICB结合,在CT26模型中显著提高了疗效,诱导了保护性免疫力.

结论:

内OX40L/PPT非病毒基因疗法是一种有前途的局部癌症治疗方法.
结合OX40L/PPT与ICB,显著提高了抗瘤疗效.
这种方法有可能促进癌症基因疗法和治疗策略的发展.

关键词:

这是一种OX40激动剂.在OX40L中.癌症癌症癌症癌症癌症基因治疗的基因疗法基因免疫疗法是一种基因免疫疗法.非病毒性基因治疗.多重复合体是多重复合体.

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