Research And Grants

Proinflammatory Myeloid Cells with GD2.CAR as Immunotherapy for High Grade Gliomas, Including Pediatric Diffuse Midline Gliomas

High grade gliomas (HGG), including Diffuse Midline Gliomas (DMG), are highly aggressive brain cancers, with less than 5% survival at five years. DMGs are predominantly seen in children and young adults This proposal seeks to develop a novel immunotherapy to benefit these patients. Myeloid cells are white blood cells that are part of the immune system. We find that intravenous administration of immature myeloid cells lacking a protein called p50 (p50-IMC) slows the growth of HGG tumors in mouse models. p50-IMC develop into mature, activated tumor myeloid cells that direct T cells to attack the cancer. However, following p50-IMC therapy most tumors eventually progress. HGGs and DMGs express a sugar known as GD2 on their surface. To improve their efficacy, we propose to direct p50-IMC to HGG tumors by expressing a GD2-targeting chimeric antigen receptor (CAR) on the p50-IMC. We will determine the effectiveness of p50-IMC/GD2.CAR cells in a model of HGG. We will also evaluate the benefit of adding additional immunotherapy agents to GD2-targeted, activated myeloid cells, to assist them in stimulating T cells to attack the cancer cells. Upon completion of these studies, we anticipate evaluating our novel immunotherapy in clinical trials against HGGs and DMGs.