Tabriz University of Medical Sciences Advanced Pharmaceutical Bulletin 2228-5881 14 4 2024 12 30 Cell Therapy Using Anti-NKG2A Pretreated Natural Killer Cells in Patients with Hepatocellular Carcinoma 918 926 10.34172/apb.43869 EN Shirin Tavakoli https://orcid.org/0000-0001-8016-6403 Maryam Samareh-Salavati Shahrokh Abdolahi Javad Verdi Iman Seyhoun Nasim Vousooghi Mohammad Vaezi Afshin Ghaderi Ardeshir Ghavamzadeh Maryam Barkhordar https://orcid.org/0000-0002-8121-2819 Mohammad Ahmadvand https://orcid.org/0000-0002-3965-0460 Journal Article 10.34172/apb.43869 2024 10 13 2024 12 03 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. Method: 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 7×108 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 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.