title: Interleukin-15 in gene therapy of cancer.
abstract: 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.
authors.affiliation: Center for Applied Medical Research, University of Navarra, Avda Pio XII, 55; 31008 Pamplona, Spain.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Ochoa
authors.forename: Guillermo
authors.initials: G
authors.lastname: Mazzolini
authors.forename: Sandra
authors.initials: S
authors.lastname: Hervas-Stubbs
authors.forename: Miguel F
authors.initials: MF
authors.lastname: de Sanmamed
authors.forename: Pedro
authors.initials: P
authors.lastname: Berraondo
authors.forename: Ignacio
authors.initials: I
authors.lastname: Melero
mesh_terms: D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism; D015316:Genetic Therapy; D006801:Humans; D053631:Interleukin Receptor Common gamma Subunit / Q000235:genetics / Q000378:metabolism; D019409:Interleukin-15 / Q000235:genetics* / Q000378:metabolism; D053720:Interleukin-15 Receptor alpha Subunit / Q000235:genetics / Q000378:metabolism; D053646:Interleukin-2 Receptor beta Subunit / Q000235:genetics / Q000378:metabolism; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D015398:Signal Transduction
chemical_list: C507941:IL2RG protein, human; D053631:Interleukin Receptor Common gamma Subunit; D019409:Interleukin-15; D053720:Interleukin-15 Receptor alpha Subunit; D053646:Interleukin-2 Receptor beta Subunit