Low Dose Radiation by Lutetium-177 Abrogates NK-92 Cell Proliferation without Compromising Cytotoxicity against Prostate Cancer Cells

Laura Ordas¹, Malick Bio Idrissou², Dan Cappabianca¹, Ohyun Kwon², Bryan Bednarz^2,3, Reinier Hernandez^2,3, Quaovi H. Sodji^1,3,*
1 Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
2 Department of Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
3 Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI, USA
* Corresponding Author: Quaovi H. Sodji. Email: email

Oncology Research https://doi.org/10.32604/or.2026.083013

Received 27 March 2026; Accepted 03 September 2026; Published online 09 September 2026

Abstract

Objectives: Adoptive natural killer (NK) cell therapy is a promising “off-the-shelf” approach for advanced solid malignancies. NK-92 cells can be expanded at scale and have broad antitumor activity but require irradiation to prevent in vivo proliferation. Standard 10 Gy γ-irradiation halts NK-92 cell proliferation but rapidly reduces cytotoxicity, thereby limiting therapeutic benefit. This study evaluated whether low-dose β-particle irradiation delivered by Lutetium-177 (¹⁷⁷Lu) suppresses NK-92 cell proliferation while preserving cytotoxicity and explored its combination with radiopharmaceutical therapy (RPT). Methods: NK-92 cells were exposed to low doses of radiation delivered by ¹⁷⁷Lu and compared with equivalent doses administered by external beam radiation therapy (EBRT). Proliferation and cytotoxicity against prostate cancer cells were assessed after irradiation. We also evaluated whether ¹⁷⁷Lu pre-irradiation of tumor cells influenced NK-92-mediated cytotoxicity and expression of NK-regulatory ligands including Fas, MICA/B and HLA-E. Results: Low absorbed doses of ¹⁷⁷Lu suppressed NK-92 cell proliferation while preserving cytotoxicity, unlike equivalent EBRT doses. NK-92 cells maintained antitumor activity in the presence of ¹⁷⁷Lu. Pre-irradiated tumor cells were more susceptible to NK-92 cell killing, but this effect was not further enhanced by disruption of the NKG2A/HLA-E axis. ¹⁷⁷Lu increased tumor cell expression of Fas and MICA/B, suggesting a potential mechanism for enhanced cytotoxicity.

Keywords

Radiopharmaceutical therapy; Lutetium-177; NK-92 cell-based adoptive cell therapy; metastatic castration-resistant prostate cancer

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Low Dose Radiation by Lutetium-177 Abrogates NK-92 Cell Proliferation without Compromising Cytotoxicity against Prostate Cancer Cells

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