Shapiro RM, Birch GC, Hu G, et al. Expansion, Persistence, and Efficacy of Donor Memory-Like NK Cells Infused for Post-Transplant Relapse. Journal of Clinical Investigation. 2022; (doi: 10.1172/JCI154334).
The results of an ongoing phase I trial indicate that adoptively transferred cytokine induced memory-like (CIML) natural killer (NK) cells hold potential for the treatment of recurrence of myeloid disease following allogeneic hematopoietic cell transplantation (HCT). A donor-derived NK cell dose of 5-10 million cells/kg was administered to patients who had post-haploidentical HCT relapse of myeloid malignancies, followed by seven doses of systemic interleukin-2 (IL-2). CIML NK cell infusion facilitated a 10- to 50-fold in vivo expansion in the first six enrolled patients that was sustained for months. The infusion of CIML NK cells was well-tolerated with fever and pancytopenia were reported most often. NK cell expansion differed from how endogenous post-HCT NK cells responded to IL-2, with no reliance on cytomegalovirus viremia. Dynamic evolution of the activated CIML NK cell phenotype was revealed via immunophenotypic and transcriptional profiling, overlaid on the naturally varying range of donor NK cells. Additional studies evaluating impacts of CIML NK cells are needed to develop improvements in cell-based immunotherapies.