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<p>Invariant natural killer T (iNKT) cells, upon activation, exhibit antitumor roles by bridging innate and acquired immunity. To overcome the challenges in producing iNKT cells from patients with cancer, we previously developed allogeneic human induced pluripotent stem cell-derived iNKT (iPSC-iNKT) cells. However, the activation of iPSC-iNKT cells by glycolipid ligands remains a critical step for iNKT cell-mediated cancer therapy. To show the effect of iPSC-iNKT cell-mediated antitumor immunity, in this preclinical study, by taking advantage of a human immune cell-transplanted patient-derived xenograft model using human IL-7/15 knock-in NSG mice, we demonstrate that a combination of iPSC-iNKT cells and α-galactosylceramide-pulsed antigen-presenting cells (αGalCer/APC) induces robust antitumor effects. Single-cell analysis of tumor-infiltrating lymphocytes revealed that this combination therapy uniquely expanded tumor-reactive memory-phenotype CD4 and CD8 T cells. Taken together, upon activation by αGalCer/APC, iPSC-iNKT cells are capable of effectively inducing antitumor T cell immunity, making them a promising tool for generating personalized antitumor T cell immunity.</p>

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Preclinical efficacy of combination therapy with allogeneic induced pluripotent stem cell-derived invariant natural killer T and α-galactosylceramide-pulsed antigen-presenting cells

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月29日

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  • Takahiro Aoki,
  • Midori Kobayashi,
  • Momoko Okoshi,
  • Munechika Yamaguchi,
  • Hiroko Okura,
  • Satoko Sasaki,
  • Yoshie Sasako,
  • Sachiko Kira,
  • Yun-Hsuan Chang,
  • Nayuta Yakushiji-Kaminatsui,
  • Jafar Sharif,
  • Masashi Matsuda,
  • Masahiro Kiuchi,
  • Kiyoshi Hirahara,
  • Motoko Y. Kimura,
  • Shinichiro Motohashi,
  • Haruhiko Koseki

摘要

Invariant natural killer T (iNKT) cells, upon activation, exhibit antitumor roles by bridging innate and acquired immunity. To overcome the challenges in producing iNKT cells from patients with cancer, we previously developed allogeneic human induced pluripotent stem cell-derived iNKT (iPSC-iNKT) cells. However, the activation of iPSC-iNKT cells by glycolipid ligands remains a critical step for iNKT cell-mediated cancer therapy. To show the effect of iPSC-iNKT cell-mediated antitumor immunity, in this preclinical study, by taking advantage of a human immune cell-transplanted patient-derived xenograft model using human IL-7/15 knock-in NSG mice, we demonstrate that a combination of iPSC-iNKT cells and α-galactosylceramide-pulsed antigen-presenting cells (αGalCer/APC) induces robust antitumor effects. Single-cell analysis of tumor-infiltrating lymphocytes revealed that this combination therapy uniquely expanded tumor-reactive memory-phenotype CD4 and CD8 T cells. Taken together, upon activation by αGalCer/APC, iPSC-iNKT cells are capable of effectively inducing antitumor T cell immunity, making them a promising tool for generating personalized antitumor T cell immunity.