TY - EJOU
AU - Ordas, Laura
AU - Idrissou, Malick Bio
AU - Cappabianca, Dan
AU - Kwon, Ohyun
AU - Bednarz, Bryan
AU - Hernandez, Reinier
AU - Sodji, Quaovi H.
TI - Low Dose Radiation by Lutetium-177 Abrogates NK-92 Cell Proliferation without Compromising Cytotoxicity against Prostate Cancer Cells
T2 - Oncology Research
PY -
VL -
IS -
SN - 1555-3906
AB - 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.
KW - Radiopharmaceutical therapy; Lutetium-177; NK-92 cell-based adoptive cell therapy; metastatic castration-resistant prostate cancer
DO - 10.32604/or.2026.083013