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Single-day nonactivated IL-18-armed CAR T cells establish a durable, stemlike state with enhanced persistence - PubMed

2 hours ago
  • #Cancer Immunotherapy
  • #IL-18 Cytokine
  • #CAR T-Cell Therapy
  • Single-day nonactivated CAR T cells engineered to secrete IL-18 (CART-IL18) show robust anti-tumor efficacy in lymphoma, leukemia, and pancreatic cancer models.
  • IL-18 expression enhances CAR T-cell persistence, metabolic fitness, and resistance to exhaustion, with upregulation of IL7R, KLF2, MCL1 and suppression of PDCD1, TOX, HAVCR2.
  • Metabolomic profiling reveals improved mitochondrial bioenergetics, including increased spare respiratory capacity and accumulation of α-ketoglutarate, malate, and spermine.
  • This activation-free CAR T product aims to reduce manufacturing time (vein-to-vein) while improving potency and persistence, supporting clinical testing for refractory tumors.