| RRC ID |
85786
|
| Author |
Nishimura K, Aoki T, Kobayashi M, Takami M, Ozaki K, Ogawa K, Hongxuan W, Shimizu D, Katsumi D, Yoshizawa H, Komatsu S, Takatani T, Hirahara K, Koseki H, Hishiki T, Motohashi S.
|
| Title |
Antibody-Dependent Cellular Cytotoxicity of iPS Cell-Derived Natural Killer T Cells by Anti-GD2 mAb for Neuroblastoma.
|
| Journal |
Cancer Sci
|
| 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.
|
| Volume |
116(4)
|
| Pages |
884-896
|
| Published |
2025-4-1
|
| DOI |
10.1111/cas.70008
|
| PMID |
39916425
|
| PMC |
PMC11967243
|
| MeSH |
Animals
Antibodies, Monoclonal* / immunology
Antibodies, Monoclonal* / pharmacology
Antibody-Dependent Cell Cytotoxicity* / immunology
Cell Line, Tumor
Gangliosides* / immunology
Humans
Induced Pluripotent Stem Cells* / cytology
Induced Pluripotent Stem Cells* / immunology
Interferon-gamma / metabolism
Mice
Natural Killer T-Cells* / immunology
Neuroblastoma* / immunology
Neuroblastoma* / pathology
Neuroblastoma* / therapy
Receptors, IgG / immunology
Receptors, IgG / metabolism
Xenograft Model Antitumor Assays
|
| IF |
4.966
|
| Resource |
| Human and Animal Cells |
IMR‐32(RCB1985)
SK-N-SH(RCB0426) |
