Combination therapy of supercharged NK cells and ONC201 or ONC206 to target aggressive K27M brain tumor.

High-grade glioma tumors are the common cause of death in pediatric patients. K27M cell line is regularly used as tumor model to study diffuse intrinsic pontine glioma (DIPG) since they harbor genetic mutation in which the lysine of the histone H3 protein is replaced with a methionine. The objective of this study is to demonstrate the significance of supercharged NK (sNK) cells alone or in combination with ONC201 or ONC206 to target such aggressive pediatric brain tumor K27M. We have observed increased secretion of IFN-γ by sNK cells compared to primary IL-2-activated NK cells. Combining sNK cells with ONC201 or ONC206 further increased IFN-γ in sNK cells. When primary NK cells and sNK cells were used as effectors against the glioma tumor cell line K27M, tumor cells were found to be highly susceptible to sNK cell-mediated cytotoxicity compared to primary NK cell-mediated cytotoxicity. sNK cell-mediated cytotoxicity against K27M was significantly increased when sNK cells were combined with ONC201 and ONC206. This study suggests the potential use of sNK cells alone or in combination with ONC201 or ONC206 as therapeutic strategies in treating and preventing the recurrence of aggressive pediatric brain tumors.