We will test the efficacy of upregulating a key element of the innate immune system. In particular, we will modulate the expression of the cathelicidin gene camp, as a stand-alone therapy and as adjunct treatment to Natural Killer (NK) cell therapy. We plan to do the experimental studies using cells derived from Gunnar’s tumors: an H3K27M-mutated Diffuse Midline Glioma with two additional mutations. The cathelicidin gene encodes a unique host defense peptide called LL-37, which is powerfully immunomodulatory. The tumor micro-environment of pediatric H3K27M-mutated Diffuse Midline Gliomas is often anti-inflammatory, which would tend to reduce the activity of NK and cytolytic T cells. LL-37 may correct this. Finally, upregulation of LL-37 should also activate microglia, the macrophage cells of the brain, to help them clear away the tumor cells, leaving only healthy brain tissue behind. We also believe that NK cell therapy will be substantially less neuroinflammatory than Chimeric Antigen Receptor (CAR) T cell therapy, with a lower incidence of encephalopathy. It will also be much less costly, since donor NK cells derived from umbilical cord blood can be used, and could potentially work even without the genetic transformation that adds a Chimeric Antigen Receptor. A patent application has been filed on this novel therapy.