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Cancer science
Apr, 2025;116 (4): 884-896.

Antibody-Dependent Cellular Cytotoxicity of iPS Cell-Derived Natural Killer T Cells by Anti-GD2 mAb for Neuroblastoma.

Katsuhiro Nishimura, Takahiro Aoki, Midori Kobayashi, Mariko Takami, Ko Ozaki, Keita Ogawa, Wang Hongxuan, Daiki Shimizu, Daisuke Katsumi, Hiroko Yoshizawa, Shugo Komatsu, Tomozumi Takatani, Kiyoshi Hirahara, Haruhiko Koseki, Tomoro Hishiki, Shinichiro Motohashi
Author Information
  1. Katsuhiro Nishimura: Department of Medical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
  2. Takahiro Aoki: Department of Medical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan. ORCID
  3. Midori Kobayashi: Department of Medical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
  4. Mariko Takami: Department of Medical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
  5. Ko Ozaki: Department of Medical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
  6. Keita Ogawa: Department of Medical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
  7. Wang Hongxuan: Department of Medical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
  8. Daiki Shimizu: Department of Medical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
  9. Daisuke Katsumi: Department of Medical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
  10. Hiroko Yoshizawa: Department of Medical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
  11. Shugo Komatsu: Department of Pediatric Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
  12. Tomozumi Takatani: Department of Pediatrics, Graduate School of Medicine, Chiba University, Chiba, Japan.
  13. Kiyoshi Hirahara: Department of Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan.
  14. Haruhiko Koseki: Laboratory for Developmental Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
  15. Tomoro Hishiki: Department of Pediatric Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
  16. Shinichiro Motohashi: Department of Medical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan. ORCID
PMID: 39916425 DOI: 10.1111/cas.70008

Abstract

While antibody-dependent cellular cytotoxicity (ADCC) by anti-disialoganglioside GD2 monoclonal antibody (mAb) has succeeded in increasing the survival rate of high-risk patients with neuroblastoma, approximately 40%-50% of patients die from the disease. Recently, we developed induced pluripotent stem cell-derived natural killer T (iPS-NKT) cells, which exhibit NK-like cytotoxicity. However, whether iPS-NKT cells can induce ADCC function is unclear. Here, we investigated the ADCC of iPS-NKT cells and the efficacy of the combination treatment of anti-GD2 mAb and iPS-NKT cells against neuroblastoma. Anti-GD2 mAb enhanced the cytotoxicity and secretion of cytokines and cytotoxic granules of iPS-NKT cells, which expressed CD16 to GD2-expressing neuroblastoma cell lines. We also examined which Fcγ receptors contribute to ADCC of iPS-NKT cells. CD16 stimulation against iPS-NKT cells caused cytotoxicity and secretion of interferon-gamma, tumor necrosis factor, and granzyme B. In contrast, CD32 and CD64 stimulation did not. In vivo, the intratumor administration of anti-GD2 mAb and iPS-NKT cells significantly inhibited tumor growth compared with the other treatment groups: no treatment, anti-GD2 mAb alone, and iPS-NKT cells alone. In conclusion, iPS-NKT cells exhibit CD16-mediated ADCC, and the addition of iPS-NKT cells to anti-GD2 mAb therapy may be a potential approach for immunotherapy against neuroblastoma.

Keywords

antibody‐dependent cellular cytotoxicity anti‐GD2 monoclonal antibody induced pluripotent stem cell invariant natural killer T cell neuroblastoma

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Grants

  1. /Kashiwado Memorial Foundation for Medical Research
  2. 23K07306/Japan Society for the Promotion of Science

MeSH Term

Neuroblastoma
Humans
Antibody-Dependent Cell Cytotoxicity
Animals
Gangliosides
Antibodies, Monoclonal
Cell Line, Tumor
Mice
Induced Pluripotent Stem Cells
Natural Killer T-Cells
Receptors, IgG
Xenograft Model Antitumor Assays
Interferon-gamma

Chemicals

Gangliosides
Antibodies, Monoclonal
ganglioside, GD2
Receptors, IgG
Interferon-gamma
Journal Article
Article has an altmetric score of 1

Word Cloud

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