H. Dolstra

IL-15 transpresentation by ovarian cancer cells improves CD34 + progenitor-derived NK cell's anti-tumor functionality

Ovarian cancer (OC) is the most lethal gynecological malignancy. As high numbers of Natural Killer (NK) cells in ascites associate with improved survival, the adoptive transfer of allogeneic NK cells is an attractive therapeutic strategy. An approach to further improve NK cell expansion and anti-tumor functionality post-infusion includes IL-15 transpresentation (transIL-15), which involves surface expression of the IL-15 cytokine bound to IL-15Rα. However, others have substantiated that systemic administration of ALT/N-803, a soluble molecule mimicking transIL-15, leads to T cell-mediated rejection of the infused allogeneic NK cell product. In addition, whether transIL-15 induce superior expansion and functionality of our hematopoietic progenitor cell-derived NK cells (HPC-NK) remains understudied. Here, we propose to transfect OC cells with IL-15 and IL-15Rα mRNA and evaluate HPC-NK cell stimulation

TIGIT blockade enhances functionality of peritoneal NK cells with altered expression of DNAM-1/TIGIT/CD96 checkpoint molecules in ovarian cancer

Advanced ovarian cancer (OC) patients have a poor 5-year survival of only 28%, emphasizing the medical need for improved therapies. Adjuvant immunotherapy could be an attractive approach since OC is an immunogenic disease and the presence of tumor-infiltrating lymphocytes has shown to positively correlate with patient survival. Among these infiltrating lymphocytes are natural killer (NK) cells, key players involved in tumor targeting, initiated by signaling via activating and inhibitory receptors. Here, we investigated the role of the DNAM-1/TIGIT/CD96 axis in the anti-tumor response of NK cells toward OC. Ascites-derived NK cells from advanced OC patients showed lower expression of activating receptor DNAM-1 compared to healthy donor peripheral blood NK cells, while inhibitory receptor TIGIT and CD96 expression was equal or higher, respectively. This shift to a more inhibitory phenotype could also be induced

CD34 + progenitor-derived NK cell and gemcitabine combination therapy increases killing of ovarian cancer cells in NOD/SCID/IL2Rg null mice

Combining natural killer (NK) cell adoptive transfer with tumor-sensitizing chemotherapy is an attractive approach against recurrent ovarian cancer (OC), as OC is sensitive to NK cell-mediated immunity. Previously, we showed that CD34