Reinforcing the function of the main killer cells of the immune system in acute myeloid leukemia by interleukin-15-engineered dendritic cells.

Despite major medical advances, acute myeloid leukemia (AML) still has a poor prognosis with a 5-year survival rate of 26%. Therefore, there is a clear need for new effective therapies that can destroy remaining malignant cells, which are not killed after the standard treatment. At present, there is much interest in the use of dendritic cell (DC)-based vaccination, as this cell therapy is capable of mobilizing the patient's own immune system, resulting in the in vivo generation of an anti-tumor response without serious toxicity or side effects. However, clinical effectiveness of DC vaccines need to be further improved. A few years ago, the U.S. National Cancer Institute has named interleukin (IL-)15 as the most promising molecule for translational oncology research and for use in therapeutic cancer vaccines. The aim of this innovative research is the in vitro generation and characterization of IL 15 trans-presenting 'designer' DC with optimized immunostimulatory capacities for the induction of efficient antitumor immune responses in AML. Our hypothesis is that DC loaded with mRNA coding for IL-15 and IL-15 receptor α trans-present IL-15 and are able to induce a strong and effective anti-tumoral immune response by activating the main killer cells of the immune system. To ensure the specificity of the antitumor response, DC will also be loaded with the leukemia-associated Wilms' tumor (WT1) antigen, which is overexpressed in AML patients. Unfortunately, immune checkpoints (e.g. programmed cell death protein (PD-1/PD-L1) interactions) could impede the immunostimulatory effects of our IL 15 trans presenting DC. Therefore, decreasing the expression of the ligands of PD 1 on DC, can result in a more powerful antitumor immune response. Overall, the combination of all these modifications turns our 'designer' DC vaccine into the ideal candidate to activate the antitumor immune system to treat (leukemic) tumor cells.

Keywords:LEUKEMIA, DENDRITIC CELLS

Disciplines:Immunology, Morphological sciences, Oncology