抗 NKG2A 预处理的 NK 细胞治疗肝细胞癌患者

The activities and functions of natural killer (NK) cells are regulated by a limited repertoire of activating and inhibitory receptors. Thus, we provided a study of inhibition of the NKG2A using monoclonal antibodies (mAbs), and as a primary endpoint, we evaluated whether it can be translated to enhance adoptive NK cell immunotherapy, as the secondary endpoint, we investigated safety and feasibility.

In this study, we investigated the safety of anti-NKG2A-pretreated NK cells in improving ADCC function to manage hepatocellular carcinoma (HCC). After a conditioning regimen, we initiated a pilot study of expanded donor haploidentical NK cell infusion. 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 10 8 cells (n=3). The median follow-up was 4 months for all patients.

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 showed a relative decrease in alpha-fetoprotein (AFP) expression levels after one month.

This study demonstrated the safety and feasibility of infusing high doses of ex vivo expanded NK cells after conditioning with transient side effects.