互补的双病毒策略驱动合成标和相关的T细胞参与表达,用于内源抗原无异性免疫疗法
Zaid Taha1,2, Mathieu Joseph François Crupi3,4, Nouf Alluqmani5,6
1Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON, K1H 8L6, Canada. ztaha053@uottawa.ca.
Nature communications
|August 23, 2024
概括
工程化瘤病毒可以表达瘤抗原,从而使得像trastuzumab这样的向治疗成为可能. 这种双病毒方法增强了抗瘤免疫力和治疗以前无法治疗的癌症的疗效.
科学领域:
- 瘤学病毒学 瘤学病毒学
- 癌症免疫疗法癌症免疫疗法
- 分子工程分子工程分子工程分子工程分子工程分子分子分子分子分子分子分子分子分子分子分子分子分子分子分子分子分子分子分子分子分子分子分子分子分子分子分子分子分子分子分子分子分子分子分子分子分子分子分子分子分子分子分子分子分子分子分子分子分子分子分子分子分子分子分子分子分子分子分子分子分子
背景情况:
- 针对性抗瘤免疫疗法显示出有希望的结果,但由于目标缺失或脱落而面临阻力.
- 这限制了治疗的有效性,并排除了某些瘤的候选性.
- 开发克服耐药性的策略对于扩大免疫疗法应用至关重要.
研究的目的:
- 为了设计一种瘤性病毒,以表达截断的HER2抗原 (HER2T),用于向治疗.
- 评估HER2T表达囊泡性口腔炎病毒 (VSVΔ51) 与基于trastuzumab的疗法结合的疗效.
- 评估一种结合VSVΔ51-HER2T与HER2向T细胞激活剂的双病毒策略,以增强抗瘤免疫力.
主要方法:
- 工程VSVΔ51表达一个缺少信号能力的截断HER2 (HER2T).
- 评估感染细胞上的HER2T表面表达.
- 在体外,外生和体内模型中评估trastuzumab emtansine的治疗疗效.
- 在体内研究中将VSVΔ51-HER2T与表达HER2向T细胞参与者的瘤性疫苗病毒结合起来.
主要成果:
- 在感染细胞表面上,VSVΔ51有效地表达了HER2T,模拟了HER2阳性状态.
- 激素HER2T的表达使得得使用trastuzumab emtansine能够有效治疗.
- 双病毒策略在小鼠体内表现出强大的疗效.
- 该组合利用CD3+T细胞透来增强抗瘤免疫力.
结论:
- 瘤病毒可以被设计成表达瘤抗原,克服对向疗法的耐药性.
- 这种方法提高了与现有的抗体 - 药物结合物和T细胞参与剂的兼容性.
- 将瘤微环境与瘤解毒病毒调整为改善癌症治疗结果提供了一个有希望的策略.
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