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CD34-TRAIL+ cells are an experimental cell therapy consisting of hematopoietic stem and progenitor cells (CD34+) engineered via adenoviral transduction to express membrane-bound tumor necrosis factor-related apoptosis-inducing ligand (mTRAIL). Developed by researchers at the Fondazione IRCCS Istituto Nazionale Tumori Milano, this approach utilizes the natural ability of CD34+ cells to home to tumor sites and the tumor microenvironment. Once at the site, the expressed mTRAIL interacts with death receptors (TRAIL-R1 and TRAIL-R2) on the surface of both malignant cells and tumor endothelial cells, inducing apoptosis and causing vascular damage. This dual mechanism of action—targeting both the tumor cells directly and the supporting vasculature—has shown efficacy in preclinical models of non-Hodgkin lymphoma and multiple myeloma. The therapy's activity can be potentiated by combination with Akt inhibitors like perifosine, which upregulate TRAIL receptor expression on target cells.
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