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The following is a summary of “First-in-human evaluation of memory-like NK cells with an IL-15 super-agonist and CTLA-4 blockade in advanced head and neck cancer,” published in the February 2025 issue of Journal of Hematology & Oncology by Shapiro et al. 

Researchers conducted a retrospective study on cytokine-induced memory-like natural killer (CIML NK) cells with an IL-15 super-agonist (N-803) as a novel treatment for relapsed/refractory head and neck cancer.  

They conducted a phase I trial using a 3+3 dose de-escalation design to evaluate haploidentical CIML NK cells with N-803 ± ipilimumab (IPI) in relapsed/refractory head and neck cancer after a median of 6 prior therapies. They assessed safety as the primary endpoint and performed high-resolution immunophenotypic and transcriptional profiling of NK cells and their interacting partners in vivo. 

The results showed dose-limiting toxicity (DLT) in 1/10 patients. Transient disease control is correlated with donor NK cell expansion, which occurs regardless of IPI. CIML NK cells with N-803 and IPI led to early NK cell proliferation, Treg:Tcon contraction, rapid CD8⁺ T-cell recovery, and accelerated donor NK cell rejection. 

Investigators found CIML NK cells with N-803 and IPI to be safe and linked to increased NK cell proliferation. However, reduced HLA-mismatched NK cell persistence limited the therapy’s effectiveness in clinical trials. 

Source: jhoonline.biomedcentral.com/articles/10.1186/s13045-025-01669-3#Abs1