Research And Grants

Targeting macrophages to improve the survival of DIPG

Diffuse Intrinsic Pontine Glioma (DIPG) is a type of high-grade pediatric glioma (pHGG) that remains uniformly fatal in 2020, represents the leading cause of death for pediatric brain tumor patients, and for which the standard of care has not improved in over 50 years. Improvements in outcomes require the identification of novel vulnerabilities that could be therapeutically targeted. We have identified a subset of cells from blood (myeloid cells) that enter DIPG and facilitate its growth. These cells also suppress the ability of T-cells to eliminate cancer. 

Approximately one-third (12 out of 36) of currently open clinical trials for DIPG primarily evaluate novel immunotherapy approaches, highlighting an urgent need to dissect the molecular mechanisms that regulate the immune microenvironment in DIPG, particularly these immunosuppressive myeloid cells from the blood.
We identified two drugs that effectively prevent infiltration of these blood myeloid from the blood by combining one FDA-approved drug (Maraviroc) and another currently used in many clinical trials (CCX872). If proven effective in our animal models, together with our long-term collaborator co-Investigator here at Mount Sinai - Dr. Oren Becher, we will initiate a clinical trial to treat children with DIPG using this drug combination.