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Abstract Details
Cell Therapy Using Anti-NKG2A Pretreated Natural Killer Cells in Patients with Hepatocellular Carcinoma.
Tavakoli, Shirin (S);Samareh-Salavati, Maryam (M);Abdolahi, Shahrokh (S);Verdi, Javad (J);Seyhoun, Iman (I);Vousooghi, Nasim (N);Vaezi, Mohammad (M);Ghaderi, Afshin (A);Ghavamzadeh, Ardeshir (A);Barkhordar, Maryam (M);Ahmadvand, Mohammad (M);
PURPOSE: 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.
METHODS: 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 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 showed a relative decrease in alpha-fetoprotein (AFP) expression levels 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.
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