First-in-Human Study of IL15–Activated Cytokine-Induced Killer Cells After Allogeneic HCT Shows Durable Remission and Serotherapy-Associated Immune Reconstitution in Leukemia

作者：Eva Rettinger, Dirk Heckl, Martin Hutter, Emilia Salzmann-Manrique, Marie Luedtke, Sabine Huenecke, Melanie Bremm, Claudia Cappel, Gesine Bug, Johann Greil, Roland Meisel, Eva Maria Wagner-Drouet, Hubert Serve, Tayfun Güngör, Jan-Henning Klusmann, Thomas Klingebiel, P. Bader, Halvard Bonig · 发表于：Journal of Clinical Oncology · 年份：2026 · DOI：10.1200/jco-25-01966 · 研究领域：Immune Cell Function and Interaction、CAR-T cell therapy research、IL-33, ST2, and ILC Pathways

PURPOSE: Patients with high-risk (HR) leukemia remain at substantial risk of early relapse, treatment-related toxicity, and poor survival, underscoring the need for effective relapse prevention therapies. To our knowledge, this first-in-human, disease burden-guided study evaluated the feasibility, safety, and efficacy of donor-derived allogeneic interleukin-15-activated cytokine-induced killer cells (IL15-CIK) combining T-cell and natural killer cell properties for post-transplant disease control. METHODS: In a prospective, multicenter phase I/II trial (EudraCT 2013-005446-11) and an identically designed pilot study, 53 adult and pediatric patients with HR leukemia received 56 courses of IL15-CIK monotherapy after human leukocyte antigen (HLA)-matched or HLA-mismatched transplantation. Treatment intent was categorized as consolidation (13%), preemptive (61%), or salvage (27%) with 169 infusions administered as a single dose (29%) or according to adaptable dose-escalation regimens (71%). RESULTS: Acute graft-versus-host disease (GVHD) grades 1-2 and grade 3 occurred in 27% and 4% of cases, respectively; no extensive chronic GVHD or treatment-related mortality was observed. IL15-CIK-associated adverse events were predominantly mild. Disease clearance, assessed by the cumulative incidence of complete molecular remission, peaked at day 700, reaching 74% in the preemptive and 13% in the salvage setting. The five-year progression-free survival was 50% overall and highest (69%) in p...