Ferritin aggregation cell engager for CAR T avidity engineering against refractory leukemias
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 recognit
Content
# Ferritin aggregation cell engager for CAR T avidity engineering against refractory leukemias
*Published: 2026 Apr 2*
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