2. Academic Validation
  3. Ferritin aggregation cell engager for CAR T avidity engineering against refractory leukemias

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

  • Cell. 2026 Apr 2;189(7):1942-1956.e26. doi: 10.1016/j.cell.2026.02.005.
Feng Li 1,  Yuxing Hu 2,  Yan Wang 1,  Xiao Zhang 1,  Shaowei Qiu 3,  Xiaoming Hu 1,  Wenjing Wang 1,  Shuang Wang 1,  Peilin Guo 4,  Cui Song 1,  Huaiji Wang 4,  Changhao He 5,  Jie Sun 6,  Di Yu 7,  Shuhua Yi 3,  Jun Wei 3,  Feifan Liu 1,  Caopei Zheng 1,  Jianxiang Wang 8,  Yuhua Li 9,  Guanghui Ma 10,  Wei Wei 11
Affiliations

Affiliations

  • 1 State Key Laboratory of Biopharmaceutical Preparation and Delivery, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, P.R. China; State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, P.R. China.
  • 2 Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, P.R. China.
  • 3 State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Tianjin Institutes of Health Science, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, P.R. China.
  • 4 State Key Laboratory of Biopharmaceutical Preparation and Delivery, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, P.R. China; State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, P.R. China; School of Chemical Engineering, University of Chinese Academy of Sciences, Beijing, P.R. China.
  • 5 Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA, USA.
  • 6 Department of Cell Biology, Zhejiang University School of Medicine, Hangzhou, P.R. China.
  • 7 The University of Queensland Diamantina Institute, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.
  • 8 State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Tianjin Institutes of Health Science, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, P.R. China. Electronic address: [email protected].
  • 9 Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, P.R. China. Electronic address: [email protected].
  • 10 State Key Laboratory of Biopharmaceutical Preparation and Delivery, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, P.R. China; State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, P.R. China; School of Chemical Engineering, University of Chinese Academy of Sciences, Beijing, P.R. China. Electronic address: [email protected].
  • 11 State Key Laboratory of Biopharmaceutical Preparation and Delivery, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, P.R. China; State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, P.R. China; School of Chemical Engineering, University of Chinese Academy of Sciences, Beijing, P.R. China. Electronic address: [email protected].
PMID: 41806835 DOI: 10.1016/j.cell.2026.02.005
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.

Keywords

CAR T cell; avidity engineering; cell engager; ferritin; leukemia.

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