Interleukin-15 (IL-15) exerts powerful stimulatory effects on lymphocyte subsets that result in antiviral and antitumoral
activities. The functions of this cytokine are mainly mediated in a cell-to-cell contact fashion termed IL-15
trans-presentation. This function is mediated by a cell which tethers IL-15 to its plasmatic membrane complexed to IL-15
receptor alpha (IL-15Rα). Such surface complexes interact with interleukin-2 receptor beta and gamma on the adjacent
cell to elicit signaling. Unlike interleukin-2, IL-15 protects from activation-induced cell death and does not promote regulatory
cells. These features underlie its activity against transplanted tumors and its adjuvanticity in tumor and viral vaccines.
The GMP-manufactured recombinant protein is undergoing clinical trials but its rapid renal clearance calls for biotechnological
strategies to increase molecular weight and ensure IL-15Rα trans-presentation. Since early efforts with stable
transfected tumor cells, IL-15 has been tested in a variety gene therapy approaches. Those mainly include transfer of
expression cassettes to tumor cells, T cells, dendritic cells, vaccination sites and the liver as a biofactory organ. Detailed
mechanistic knowledge of IL-15 biology is envisaged to make the most of a powerful immunotherapeutic tool ranked as
one of the most promising for cancer immunotherapy.
Keywords: Cancer, gene therapy, interleukin-15, immunotherapy, cytokine, interleukin 2, tumors, T cells
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