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开发一种新型,高效的瘤性简单疹病毒1型平台,配备两个不同的重定位模式

Hyun-Yoo Joo¹, Hyunjung Baek¹, Chun-Seob Ahn¹

¹Gencellmed Inc., Korea Institute of Radiological and Medical Sciences, Room 302 Research Building #3, Seoul, Republic of Korea.

Molecular therapy. Oncology

|April 10, 2024

概括

一种新的双重重定位的瘤性简单性疹病毒 (oHSV) 通过特定的抗体有效地准癌细胞. 这种工程病毒的单剂量消除了小鼠的瘤,显示了癌症治疗的前景.

科学领域:

瘤治疗性病毒疗法
癌症免疫疗法癌症免疫疗法
病毒载体工程是病毒载体工程.

背景情况:

瘤性简单疹病毒 (oHSV) 显示出对癌症治疗的潜力.
将oHSV向瘤特异性抗原可以提高疗效和安全性.
当前的oHSV平台可能缺乏特异性和高效的系统性交付.

研究的目的:

开发一种新的,双重重定向的oHSV平台,用于增强癌细胞向.
为了利用单链抗体 (scFvs) 获得双受体特异性.
评估工程oHSV的体外和体内疗效和安全性.

主要方法:

设计了一种双重重定位的oHSV,将scFvs纳入糖蛋白H和双特异适配器.
在保持疹病毒入口媒介体 (HVEM) 结合的同时,准了nectin-1相互作用.
经过测试的上皮细胞粘附分子 (EpCAM) 和人类表皮生长因子受体2 (HER2) 特定的scFvs.
在体外和体外模型中评估感染和传播.

主要成果:

在体外实现了剂量依赖的,针对受体的特定感染.
与单个重定位病毒相比,证明病毒传播的增强.
通过EpCAM特定的oHSV.表现出有效的体内感染和瘤消除.
在免疫能力较强的小鼠中没有观察到明显的毒性.

结论:

双重重定位的oHSV平台提供了强大而通用的癌细胞向.
这种oHSV的全身传递显示出有效和安全的癌症治疗方法的希望.
这种方法可以对表达所需抗原的癌细胞进行特定向.

关键词:

在 EpCAM 中使用 EpCAM.MT: 定期发行定期发行双重定位的目标是双重目标.gHgH 在这里.葡萄糖蛋白H H oHSV-1 是一个瘤性简单疹病毒1型自定位适配器自定位适配器

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