2. Academic Validation
  3. Anti-transferrin receptor antibody (JST-TFR09/PPMX-T003) induces ferroptosis in adult T-cell leukemia/lymphoma (ATLL) cells

Anti-transferrin receptor antibody (JST-TFR09/PPMX-T003) induces ferroptosis in adult T-cell leukemia/lymphoma (ATLL) cells

  • Biochem Biophys Res Commun. 2025 Apr 5:756:151564. doi: 10.1016/j.bbrc.2025.151564.
Yanuar Rahmat Fauzi 1,  Shingo Nakahata 2,  Kazuya Shimoda 3,  Tadashi Matsuura 4,  Shinji Hagiwara 4,  Kentaro Inoue 5,  Hiroshi Moritake 6,  Kazuhiro Morishita 7
Affiliations

Affiliations

  • 1 Division of Pediatrics, Department of Developmental and Urological-Reproductive Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan; Department of Biochemistry and Biomolecular, Faculty of Medicine, Brawijaya University, Malang, Indonesia.
  • 2 Division of HTLV-1/ATL Carcinogenesis and Therapeutics, Joint Research Center for Human Retrovirus Infection, Kagoshima University, Kagoshima, Japan.
  • 3 Division of Hematology, Diabetes, and Endocrinology, Department of Internal Medicine, University of Miyazaki, Miyazaki, Japan.
  • 4 Perseus Proteomics Inc, Chuo-ku, Tokyo, Japan.
  • 5 Faculty of Engineering, University of Miyazaki, Miyazaki, Japan.
  • 6 Division of Pediatrics, Department of Developmental and Urological-Reproductive Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
  • 7 Division of Pediatrics, Department of Developmental and Urological-Reproductive Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan. Electronic address: kmorishi@med.miyazaki-u.ac.jp.
PMID: 40086360 DOI: 10.1016/j.bbrc.2025.151564
Abstract

Previously, we developed a complete human IgG TFR1 antibody (JST-TFR09/PPMX-T003) that showed a potentially practical therapeutic effect against adult T-cell leukemia/lymphoma (ATLL) in vitro and in vivo. In the present study, to elucidate the molecular mechanism underlying ATLL cell death induced by anti-TFR1 antibodies, we performed comprehensive gene expression analysis and mass spectrometry on ATLL cells treated with PPMX-T003 antibody. These results suggest that PPMX-T003 antibody treatment of ATLL cell lines induces Ferroptosis mediated by ferritin degradation. PPMX-T003 antibody-treated ATLL cell lines showed a decrease in ferritin proteins, an increase in ferrous iron (Fe2+), Reactive Oxygen Species (ROS) generation, and malondialdehyde as induction of lipid peroxidation. Moreover, treatment with a Ferroptosis inhibitor (ferroportin-1) inhibited the cell death induced by PPMX-T003 antibody in ATLL cells. Furthermore, NCO4A and LC3-II were induced following antibody treatment, and ferritin degradation was inhibited by lysosomal inhibitors, suggesting that ferritin degradation depends on autolysosomal system activation. Here, we introduce Ferroptosis as one of the potential mechanisms of PPMX-T003 antibody, which is promising for future therapeutic antibodies targeting a wide range of leukemia and cancers, including ATLL.

Keywords

Adult T-cell leukemia/lymphoma; Anti-transferrin Receptor-1 antibody; Ferroptosis.

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