Adjuvant therapy using ex vivo-expanded allogenic natural killer cells in hepatectomy patients with hepatitis b virus related solitary hepatocellular carcinoma: Mg4101 study

Backgrounds/Aims: Fewer reports have been published regarding hepatectomy patients with solitary hepatocellular carcinoma (HCC) who received immunotherapeutic agents as adjuvant therapy. We evaluated the safety and efficacy of ex vivo-expanded allogenic natural killer (NK) cells in those patients with modified International Union Against Cancer (UICC) stage T3. Methods: From August 2014 to October 2015, five patients who underwent hepatic resection received ex vivo-expanded allogenic NK cells. Patients received five rounds of NK cells (2-3×10⁷ cells/kg) at postoperative 4, 6, 8, 12, and 16 weeks. This study is registered with ClinicalTrials.gov, number NCT02008929. Results: The median age of the five patients (three men and two women) was 44.8 years (range, 36-54 years). All had hepatitis B virus-related HCC, and the median tumor size was 2.2 cm (range, 2.1-8.2 cm). None of the patients had any adverse events. HCC recurrence developed in two patients at one year after hepatic resection, but four patients were alive at 3 years. The two recurrence-free patients showed a higher ratio of CD8+ T lymphocyte populations before and after administration of ex vivo-expanded allogenic NK cells compared with the three patients who experienced recurrence. Conclusions: Immunotherapy using ex vivo-expanded allogenic NK cells in hepatectomy patients can be used safely. Further studies should be investigated for efficacy. (Ann Hepatobiliary Pancreat Surg 2021;25:206-214).