Cell Therapy Using Anti-Nkg2a Pretreated Natural Killer Cells in Patients With Hepatocellular Carcinoma Publisher



Tavakoli S¹ ; Samarehsalavati M¹ ; Abdolahi S² ; Verdi J¹ ; Seyhoun I¹ ; Vousooghi N¹ ; Vaezi M³ ; Ghaderi A⁴ ; Ghavamzadeh A³ ; Barkhordar M^{1, 3} ; Ahmadvand M³ Show Affiliations
Source: Advanced Pharmaceutical Bulletin Published:2024

Abstract

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. © 2024 The Author (s).