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通过双重向的CAR-T疗法推进肝癌治疗

Ze Yang^1,2,3, Chao Cheng⁴, Zhongliang Li^3,5

¹Interventional Medical Treatment Department, Guangzhou First Pepople's Hospital, the Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China.

Journal of nanobiotechnology

|June 23, 2025

概括

这项研究引入了一种双向的化学抗原受体 (CAR) -T细胞治疗肝癌的方法. 将glypican-3 (GPC3) CAR-T细胞与针对alpha-fetoprotein (AFP) 的双特异性T细胞参与者结合起来,可以增强抗瘤活性.

科学领域:

免疫治疗是一种免疫疗法.
在瘤学瘤学.
生物技术是生物技术.

背景情况:

化学抗原受体 (CAR) -T细胞疗法针对甘氨酸-3 (GPC3) 显示出对肝细胞癌 (HCC) 的承诺.
仅针对细胞表面抗原的CAR-T细胞疗效存在局限性.
细胞内α-fetoprotein (AFP) 是一种肝癌生物标志物,表现为HLA-A*02:01.

研究的目的:

为增强肝细胞癌 (HCC) 治疗开发一种双向的CAR-T细胞策略.
为了设计T细胞受体 (TCR) 模仿细胞内AFP向的抗体.
为了改善CAR-T细胞的增殖,持久性和HCC的抗瘤活性.

主要方法:

设计GPC3 CAR-T细胞以分泌两种特异性T细胞吸引剂 (BiTE),准HLA-A*02:01受限制的AFP表位.
开发出TCR模仿抗体,用于高亲和度向AFP表位.
在实验室和体内对HCC模型进行评估的双向CAR-T细胞疗效.

主要成果:

双重向策略显著增强了CAR-T细胞的增殖和持久性.
在HCC细胞中观察到改善的细胞因子表达和强大的抗瘤活性.
对具有低GPC3和AFP表达的HCC细胞具有已证明的疗效.

结论:

双重向的CAR-T细胞策略为肝癌治疗提供了一个有前途的方法.
这种创新疗法可以克服单抗原向的局限性.
对于肝细胞癌患者来说,可能会有更有效的治疗选择.

关键词:

阿尔法-胎儿蛋白是一种α-胎儿蛋白.两种方式的BiTE BiTE 在CART-T中,我们可以使用CAR-T.在Glypican-3中使用.肝癌是一种肝癌.

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