{
  "id": 7877802,
  "title": "Scalable expansion of human iNKT cells: single-cell profiling and in vivo control of GvHD with preserved GvL activity",
  "url": "https://urgent.news/2026/09/16/scalable-expansion-of-human-inkt-cells-single-cell-profiling-and-in",
  "topic": "science",
  "section": "Science",
  "published": "2026-09-16T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.09.11.750594v1?rss=1"
  },
  "original_language": "en",
  "account": "Invariant natural killer T (iNKT) cells have the potential to reduce graft-versus-host disease (GVHD) following hematopoietic stem cell transplantation (HSCT), but their limited presence in peripheral blood hinders therapeutic development. Current methods for expanding human iNKT cells, mainly using IL-2, rely on prior iNKT-cell sorting, take 6-8 weeks, and primarily expand CD4+ iNKT cells. However, CD4- iNKT cells are more effective at controlling GVHD and regulating antigen-presenting cells and T-cell activation.\n\nResearchers have developed a scalable culture system that can directly expand human CD4- iNKT cells from total peripheral blood mononuclear cells (PBMCs) using alpha galactosylceramide (alpha-GalCer) and optimized cytokine conditions. IL-15 proved to be the most effective cytokine in this process. The 14-day protocol yielded approximately 3.8 million iNKT cells from just 2 million PBMCs, with 74% of them being CD4- iNKT cells.\n\nSingle-cell transcriptomic profiling revealed eight major iNKT subsets, various differentiation trajectories during expansion, and distinct transcriptional programs associated with IL-2 versus IL-15. iNKT cells expanded with IL-15 displayed enhanced abilities to kill monocyte-derived dendritic cells and leukemic cells in vitro. Furthermore, these iNKT cells controlled xeno-GVHD and preserved graft-versus-leukemia (GVL) activity in preclinical mouse models.\n\nThis innovative platform enables the reproducible production of human CD4- iNKT cells at a clinically relevant scale, positioning IL-15-expanded iNKT cells as a promising immunotherapy candidate for allogeneic HSCT.",
  "summary": "Invariant natural killer T (iNKT) cells can limit graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation (HSCT), but their scarcity in peripheral blood limitstherapeutic development. Current clinical-grade human iNKT expansion protocols mainly rely on IL-2, require prior iNKT-cell sorting, last 6-8 weeks, and predominantly expand CD4+ iNKT cells, whereas human CD4- iNKT…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}