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Cell Therapy Using Anti-NKG2A Pretreated Natural Killer Cells in Patients with Hepatocellular Carcinoma
Shirin Tavakoli1, Maryam Samareh-Salavati1, Shahrokh Abdolahi2
1Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
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 7×108 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.
Insights
This study shows that inhibiting NKG2A with monoclonal antibodies is safe and feasible for enhancing adoptive natural killer (NK) cell immunotherapy in liver cancer patients.
Area of Science:
- Immunology
- Oncology
- Cell Therapy
Background:
- Natural killer (NK) cells are crucial for immune surveillance, regulated by activating and inhibitory receptors.
- NKG2A is an inhibitory receptor on NK cells that can limit their anti-tumor activity.
Purpose of the Study:
- To evaluate the inhibition of NKG2A using monoclonal antibodies (mAbs) for enhancing adoptive NK cell immunotherapy.
- To assess the safety and feasibility of this approach in patients with hepatocellular carcinoma (HCC).
Main Methods:
- A pilot study involving infusion of expanded donor haploidentical NK cells pretreated with anti-NKG2A antibodies.
- Patients received a conditioning regimen (fludarabine/cyclophosphamide) followed by NK cell infusions.
- NK cells were activated with IL-2 and infused at a dose of 7×10^8 cells on days 0, +5, and +10.
Main Results:
- All patients survived the follow-up period (median 4 months).
- Two patients experienced disease progression with increased tumor size.
- A consistent decrease in alpha-fetoprotein (AFP) levels was observed in all patients after one month.
Conclusions:
- Infusion of high-dose ex vivo expanded NK cells following conditioning is safe and feasible.
- Transient side effects were observed.
- Targeting NKG2A shows potential for improving adoptive NK cell immunotherapy, though further investigation is needed for efficacy.
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