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专门编辑癌症西奥甘以通过阿普塔默-酶奇默体增强体内免疫疗法

Qin Liu¹, Hang Xing², Mengyi Xiong¹

¹Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan University, 410082, Changsha, Hunan, P. R. China.

Angewandte Chemie (International ed. in English)

|September 26, 2024

概括

葡萄糖免疫检查点消除 (glycoICE) 疗法使用aptamer-enzyme奇默来编辑瘤细胞表面的sialoglycans,增强癌症免疫疗法. 这种新的方法破坏了免疫逃逸,提高了治疗效率,副作用最小.

科学领域:

生物化学生物化学
免疫学免疫学免疫学
在瘤学瘤学.

背景情况:

免疫检查点阻塞 (ICB) 疗法在癌症治疗中表现有前途,但由于对免疫逃避途径的向有限,其反应率不够理想.
目前的ICB疗法没有解决癌细胞使用的多方面的免疫逃避策略.

研究的目的:

开发一种新的免疫疗法策略,即糖免疫检查点消除 (glycoICE),用于增强癌症治疗.
为了创建一个多功能的阿普坦酶-酶合体 (ApEC) 平台,用于向瘤细胞上的化甘编辑.

主要方法:

通过大规模生产的一步生物对称程序生成阿普坦酶仿真体 (ApECs).
用APEC对癌细胞进行有针对性的脱氧化,以破坏西亚甘-西格莱克轴,并激活免疫细胞.
利用Apec的瘤选择性向来最大限度地减少对正常组织的非向效应.

主要成果:

ApECs有效地向和脱氧化癌细胞,破坏西亚糖-西格莱克轴.
葡萄糖ICE疗法证明增强了免疫细胞的激活,并提高了免疫治疗的疗效.
观察到ApECs的高瘤选择性,最大限度地减少了副作用.

结论:

甘ICE疗法代表了一种新的方法,通过向sialoglycans来克服癌症免疫逃避.
ApEC为基于DNA的药物开发和癌症免疫治疗中的潜在临床应用提供了一个多功能平台.
这一策略通过破坏特定的瘤相关的糖结构来提高免疫疗法的有效性.

关键词:

亚普坦 - 酶奇梅拉 - 亚普坦免疫疗法是一种免疫疗法.核酸是核酸中的一种.类甘油是一种.

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