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基于GPC3的循环RNA疫苗通过激活自适应性免疫反应来抑制肝细胞癌的进展

Yifan Jiang^1,2,3,4, Yu Li^1,2,3,4, Tong Wu^1,2,3

¹Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang Province, Hangzhou, P.R. China.

Hepatology (Baltimore, Md.)

|November 7, 2025

概括

一种针对Glypican-3 (GPC3) 的新型循环RNA (circRNA) 癌症疫苗显示,肝细胞癌 (HCC) 的稳定性得到改善,抗瘤免疫力更强. 将其与托尔类受体4 (TLR4) 激动剂相结合,通过重编程瘤微环境,进一步提高了疗效.

科学领域:

在瘤学瘤学.
免疫学免疫学免疫学
生物技术是生物技术.

背景情况:

使者RNA (mRNA) 癌症疫苗面临的挑战包括不稳定性和低效的输送.
循环RNA (circRNA) 在稳定性和抗原呈现方面为癌症疫苗提供了潜在的优势.
格利皮坎-3 (GPC3) 是肝细胞癌 (HCC) 中关键的瘤相关抗原.

研究的目的:

开发和评估一种基于circRNA的癌症疫苗,针对HCC的GPC3.
评估疫苗的稳定性,免疫性和抗瘤功效.
研究circGPC3疫苗与托尔类受体4 (TLR4) 激动剂的联合治疗.

主要方法:

设计了一个编码GPC3.3的circRNA疫苗.
在HCC小鼠模型中使用了有或没有TLR4激动剂的circGPC3疫苗.
利用多重免疫光学,单细胞测序,空间转录组学和质量细胞测量来分析瘤微环境 (TME).

主要成果:

与mRNA疫苗相比,circGPC3疫苗表现出持续的抗原产生和增强的抗瘤免疫反应.
与TLR4激动剂的联合治疗显著抑制了HCC的瘤进展.
从机制上讲,治疗改善了TME内的抗原呈现和T细胞激活.

结论:

对于HCC,circGPC3癌症疫苗比传统的mRNA疫苗更有效.
与TLR4激动剂的结合破坏了HCC的免疫耐受性,这是一个有前途的治疗策略.

关键词:

在Glypican-3中使用.癌症免疫疗法免疫疗法癌症疫苗疫苗癌症疫苗圆形的RNARNA是一个圆形的RNA.传递 RNA 的信使 RNA.

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