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向B7H3的CAR T细胞表现出强大的临床前活性,对抗AML和ESCC

Chang Liu¹, Jinping Zhao¹, Xuhua Zhang²

¹Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.

International immunopharmacology

|November 10, 2025

概括

针对B7H3的工程T细胞显示出治疗急性髓性白血病 (AML) 和食道状细胞癌 (ESCC) 的前景. 这种新型的仿真抗原受体 (CAR) -T疗法在临床前模型中证明了安全性和有效性,提供了新的治疗策略.

科学领域:

免疫治疗是一种免疫疗法.
在瘤学瘤学.
细胞工程细胞工程

背景情况:

化学抗原受体 (CAR) -T细胞疗法在B细胞淋巴瘤中取得了成功,但在急性髓性白血病 (AML) 和固体瘤中面临挑战.
免疫调节分子B7H3在AML和食道状细胞癌 (ESCC) 中异常表达,与瘤进展相关.

研究的目的:

开发和评估针对B7H3的CAR-T细胞,用于AML和ESCC的潜在治疗.
评估这些工程T细胞的体外和体内安全性和有效性.

主要方法:

使用人性化的抗B7H3抗体片段 (A172-hu4) 构建了针对B7H3的CAR-T细胞.
在AML和ESCC细胞系和异种移植小鼠模型中评估了CAR-T细胞亲和力,细胞毒性,细胞因子产生 (IFN-γ,IL-2) 和瘤抑制.

主要成果:

在体外,A172-hu4-CAR-T细胞表现出显著的IFN-γ和IL-2生产和强大的细胞毒性作用.
用A172-hu4-CAR-T细胞治疗导致AML和ESCC小鼠模型中明显的瘤抑制.
在治疗小鼠的主要器官中没有观察到明显的毒性反应.

结论:

在AML和ESCC中,B7H3是CAR-T治疗的可行标.
针对B7H3的CAR-T细胞显示了临床前的安全性和有效性,支持进一步的临床开发.
这种方法提供了一种新的策略,以推进对具有挑战性的癌症的CAR-T疗法.

关键词:

急性骨髓性白血病 (AML) 是一种急性骨髓性白血病.B7H3 B7H3 B7H3 B7H3 B7H3 B7H3 B7H3 B7H3 B7H3 B7H3 B7H3 B7H3 B7H3 B7H3 B7H3 B7H3 B7H3 B7H3 B7H3 B7H3 B7H3 B7H3 癌症免疫疗法癌症免疫疗法化学抗原受体的化学抗原受体食管状细胞癌的癌症

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