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This investigational cell therapy protocol, developed by the National Heart, Lung, and Blood Institute (NHLBI), involves the adoptive transfer of ex vivo expanded autologous natural killer (NK) cells in combination with the proteasome inhibitor bortezomib. The therapeutic strategy relies on the ability of bortezomib to sensitize metastatic solid tumor cells and hematological malignancies to NK cell-mediated cytotoxicity, specifically through the TNF-related apoptosis-inducing ligand (TRAIL) pathway. Patients undergo lymphodepletion with pentostatin prior to the infusion of their own expanded NK cells, followed by interleukin-2 administration to support cell persistence and activity. This approach aims to overcome tumor resistance mechanisms and enhance the anti-tumor efficacy of innate immune effector cells.
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