4-1BB Antibody Enhances Cytotoxic Activity of Natural Killer Cells Against Prostate Cancer Cells Via NKG2D Agonist Combined with IL-27

Aims: To enhance the cytotoxicity of natural killer (NK) cells against prostate cancer cells via NKG2D agonist, with 4-1BB antibody and IL-27 combination. Materials & methods: FACS was used to detect degranulation and cell surface receptors in NK cells isolated from healthy donors. Cytokine concentrations were measured using ELISA. NK-cell cytotoxicity was analyzed using Cell Counting Kit-8. Results: NKG2D agonist, 4-1BB antibody and IL-27 combination treatment improved the activating receptor expression and IFN-γ and TNF-α secretion but decreased the suppressive receptor CD158a expression and IL-10 secretion in NK cells. The combined treatment enhanced NK-cell cytotoxicity against both PC3 and DU145 cells with concurrent enhanced STAT3 activation. Conclusion: 4-1BB antibody and IL-27 improved NKG2D agonist function in NK cells against prostate cancer cells.