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: Maria C Ochoa, Guillermo Mazzolini, Sandra Hervas-Stubbs, Miguel F de Sanmamed, Pedro Berraondo, Ignacio Melero
• Journal: Current gene therapy (Curr Gene Ther) Vol. 13 Issue 1 Pg. 15-30 (Feb 2013) ISSN: 1875-5631 [Electronic] United Arab Emirates
• PMID: 23157547 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• IL2RG protein, human
• Interleukin Receptor Common gamma Subunit
• Interleukin-15
• Interleukin-15 Receptor alpha Subunit
• Interleukin-2 Receptor beta Subunit

Topics

• Dendritic Cells (cytology, metabolism)
• Genetic Therapy
• Humans
• Interleukin Receptor Common gamma Subunit (genetics, metabolism)
• Interleukin-15 (genetics, metabolism)
• Interleukin-15 Receptor alpha Subunit (genetics, metabolism)
• Interleukin-2 Receptor beta Subunit (genetics, metabolism)
• Killer Cells, Natural (cytology, immunology)
• Lymphocyte Activation (drug effects, genetics, immunology)
• Neoplasms (genetics, pathology, therapy)
• Signal Transduction