中国科学院过程工程研究所魏炜团队的一项最新研究出用于CAR-T免疫工程治疗难治性白血病的铁蛋白聚集细胞接合剂。2026年3月9日出版的《细胞》杂志发表了这项成果。

基于他们对不同类型的白血病细胞和相应的CAR-T细胞都强烈表达CD71（一种铁蛋白受体）的临床见解，该团队设计了一种铁蛋白聚集细胞接合器（FACE），它可以锚定在CAR-T细胞表面，引导CAR-T细胞面对白血病细胞，并促进CAR识别同源抗原。多种白血病源性细胞和白血病源性异种移植模型的体外和体内实验表明，他们的FACE-CAR-T细胞成功地提高了治疗效果，具有良好的生物安全性，降低了克服抗原调节的抗原阈值，甚至在铁蛋白中装载化疗药物进行联合治疗。这种基因工程为提高CAR-T细胞治疗各种难治性白血病的疗效提供了一种新型、简便、通用和灵活的方法。

据悉，尽管嵌合抗原受体T（CAR-T）细胞疗法治疗白血病很有希望，但它仍然面临抗原调节的关键挑战，这引起了耐药性。

附：英文原文

Title: Ferritin aggregation cell engager for CAR T avidity engineering against refractory leukemias

Author: Feng Li, Yuxing Hu, Yan Wang, Xiao Zhang, Shaowei Qiu, Xiaoming Hu, Wenjing Wang, Shuang Wang, Peilin Guo, Cui Song, Huaiji Wang, Changhao He, Jie Sun, Di Yu, Shuhua Yi, Jun Wei, Feifan Liu, Caopei Zheng, Jianxiang Wang, Yuhua Li, Guanghui Ma, Wei Wei

Issue&Volume: 2026-03-09

Abstract: Although promising, chimeric antigen receptor T (CAR T) cell therapy for treating leukemias still faces the critical challenge of antigen modulation, which causes resistance. Building from our clinical insight that both diverse types of leukemia cells and corresponding CAR T cells strongly express CD71 (a ferritin receptor), we designed a ferritin aggregation cell engager (FACE) that can anchor to the CAR T cell surface, guide CAR T cells to face leukemia cells, and facilitate CAR recognition of cognate antigens. In vitro and in vivo experiments with diverse leukemia patient-derived cells and leukemia patient-derived xenograft models show that our FACE-CAR T cells succeed in enhancing therapeutic efficacy with good biosafety, lowering the antigen threshold for overcoming antigen modulation, and even loading chemodrugs in ferritin for combination therapy. This avidity engineering provides a neotype, facile, universal, and flexible approach for improving the efficacy of CAR T cell therapy for diverse refractory leukemias.

DOI: 10.1016/j.cell.2026.02.005

Source: https://www.cell.com/cell/abstract/S0092-8674(26)00170-4