Cell therapy using anti-NKG2A pretreated natural killer cells in patients with hepatocellular carcinoma

Background: The activities and functions of natural killer (NK) cells are controlled by a limited repertoire of activating and inhibitory NK receptors. Therefore, blocking inhibitory receptors such as NKG2A using monoclonal antibodies (mAbs) enhances tumor immunity. Method: In this study, we investigated the safety of anti-NKG2A-pretreated NK cells in improving ADCC function to manage hepatocyte carcinoma (HCC). After a conditioning regimen, we initiated a pilot study of expanded donor haploidentical NK cell infusion. The goals were to determine the safety and feasibility. Patients received a fludarabine/cyclophosphamide conditioning followed by adoptive immunotherapy with IL2–activated haploidentical NK cells. Anti-NKG2A pretreated NK cells were infused on days 0, +5, and +10 post-conditioning regimens at a dose of 7 × 108 cells (n=3). The median follow-up was 4 months for all patients. Results: Although all patients were alive at the last follow-up, two of them showed progressive disease and an increase in tumor size. In addition, all patients had a relative decrease in the expression level of an alpha-fetoprotein (AFP) after one month. Conclusion: This study demonstrated the safety and feasibility of infusing high doses of ex vivo expanded NK cells after conditioning with transient side effects.