Umbilical cord blood-derived natural killer cells: in vitro, in vivo, and clinical antitumor activity in non-small cell lung cancer (case series)

Background: Lung cancer remains a globally burdensome disease with high mortality. While current non-small cell lung cancer (NSCLC) treatments – surgery, chemotherapy, targeted therapy, and immune checkpoint inhibitor–based immunotherapy – have modestly improved outcomes, drug resistance and severe side effects limit efficacy, highlighting the urgent need for alternative therapies. Materials and methods: This study assessed the therapeutic potential of umbilical cord blood-derived natural killer (UCB-NK) cells in NSCLC via in vitro, in vivo , and clinical analyses. In vitro cytotoxicity of expanded UCB-NK cells was evaluated against NSCLC cell lines (A549, NCI-H1975) at various effector-to-target (E:T) ratios. In vivo antitumor efficacy was examined in A549-bearing NCG (NOD-Prkdcem26Cd52Il2rgem26Cd22/Gpt) mice treated with UCB-NK cells combined with IL-2. Additionally, a clinical case series of five NSCLC patients receiving multimodal therapy plus UCB-NK infusions was evaluated. Results: In vitro , expanded UCB-NK cells showed dose-dependent cytotoxicity against NSCLC cell lines, achieving up to 80% tumor cell lysis at E:T ratios of 5:1 and 10:1. In A549-bearing NCG mice, UCB-NK/IL-2 combination therapy significantly reduced tumor volume by 25.59% and tumor weight by 26.5% compared to IL-2 monotherapy ( P < 0.01). Clinical evaluation of five NSCLC cases receiving multimodal therapy plus UCB-NK infusions demonstrated disease stabilization. Conclusion: UCB-NK cells hold promise as an alternative therapeutic approach for NSCLC, with the potential to combine with other therapies to improve survival and quality of life. However, large-scale clinical studies are needed to verify safety and optimize treatment protocols.