2026-03-10 中国科学院（CAS）
A biomimetic platform to enhance CAR T cell therapy against leukemia (Image by LI Feng)
＜関連情報＞
- https://english.cas.cn/newsroom/headlines/202603/t20260309_1152131.shtml
- https://www.cell.com/cell/abstract/S0092-8674(26)00170-4
難治性白血病に対するCAR T親和性工学のためのフェリチン凝集細胞エンゲージャー Ferritin aggregation cell engager for CAR T avidity engineering against refractory leukemias
Feng L ∙ Yuxing Hu ∙ Yan Wang ∙ … ∙ Yuhua Li ∙ Guanghui Ma ∙ Wei Wei
Cell Published:March 9, 2026
DOI:https://doi.org/10.1016/j.cell.2026.02.005
Highlights
- A ferritin-based engager enhances CAR T avidity via CD71 without CAR redesign
- The engager lowers antigen density thresholds to overcome CAR T resistance
- Drug-loaded ferritin enables CAR T therapy combined with chemotherapy
- Therapeutic efficacy is validated across multiple leukemia PDX models
Summary
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.
