Game Changer Grant Awarded to Bilal Omer

Diffuse midline gliomas (DMG), a recently described classification that includes diffuse intrinsic pontine glioma (DIPG), are the leading cause of brain tumor deaths in children. Unfortunately, there is no cure for DMG and most children survive less than a year from diagnosis. Recent research advances have found that 80% of DMG have very high levels of a protein called GD2 on the cell surface. GD2 is an attractive target for therapies directed to fight other GD2 expressing cancers such as neuroblastoma. GD2 can be targeted using immunotherapy, which is a way of using the body’s own immune cells to kill cancer cells. For this treatment, immune cells taken from a few tablespoons of the patient’s own blood, are genetically reprogrammed to recognize and kill DMG/DIPG cancer cells. These cells, termed CAR T cells, are then given back to the patient to fight their cancer. Our laboratory has further “fueled” their anti-tumor efficacy and increased the lifespan of the GD2 targeting CAR T cells by adding another gene that provides cytokine stimulation, termed C7R. To date, we have treated 12 patients with escalating doses to determine the best dose. We have observed good tolerance to this therapy and shown the treatment to be feasible and safe. Most patients have experienced clinical improvements post-treatment, with longer responses observed with the C7R cytokine gene. In addition, two patients have seen their tumors shrink by more than 50% in response to treatment on MRI scans. The majority of patients have gone on to receive multiple treatment courses. To build on this positive experience, we aim to further enhance the efficacy of this therapy by attacking the tumor from two sides - administering the CAR T cells into the bloodstream (via intravenous infusion) as well as locally, adjacent to the tumor (via infusion into the spinal fluid, which encompasses the brain and spine). The aims of our study are to determine safety and feasibility of local delivery in combination with bloodstream treatment and to improve anti-tumor effects using this dual delivery approach. Our ultimate goal with this trial is to improve outcomes for children with these devastating brain tumors.