Phase 1 CIML-NK allogeneic NK-cell immunotherapy (IL-12/15/18–primed “memory-like” NK cells)

This first-in-human, single-site Phase 1 study at Cincinnati Children’s tests whether cytokine-induced memory-like natural killer cells (CIML-NK)—an allogeneic NK-cell product generated from a patient’s haploidentical donor apheresis—can be manufactured and infused safely for relapsed/refractory high-risk neuroblastoma during dinutuximab-based anti-GD2 therapy. The CIML-NK approach uses brief priming with IL‑12/IL‑15/IL‑18 to create “memory-like” NK cells with enhanced persistence and cytotoxicity, aiming to intensify antibody-dependent cellular cytotoxicity when paired with dinutuximab (anti‑GD2 mAb; originally developed by NCI and commercialized as Unituxin by United Therapeutics). The study is primarily a feasibility/safety platform (dose and schedule refinement, monitoring for infusion toxicity, cytokine-release–type syndromes, and graft-versus-host–type complications that are uncommon with NK cells but still monitored). It targets patients whose disease has progressed after prior intensive multimodal therapy; today’s care for R/R neuroblastoma is iterative salvage chemotherapy/chemoimmunotherapy (often irinotecan/temozolomide-based regimens) plus anti‑GD2–based combinations when tolerated, with select patients receiving MIBG radiotherapy, ALK inhibitors for ALK-altered tumors, or clinical trials. The scientific angle is a donor-derived, “trained” innate-cell add-on designed to make anti‑GD2 therapy more effective without introducing engineered receptors (e.g., CARs), potentially simplifying manufacturing relative to gene-modified cell therapies.