Research And Grants

Advancing T Cell Therapy for DMG Using Tumor-Directed Gamma Delta T Cells and TLR7/8 Agonist Immunomodulation

We propose a new type of immunotherapy for diffuse midline glioma (DMG) and using gdT cells, a type of T cell that targets cancers differently than the T cells previously used in brain tumor immunotherapies, and using a novel immune-stimulating drug that we developed. Children with DMG need new therapies because radiation therapy and chemotherapy consistently fail to cure patients. Immunotherapy, which has cured previously incurable leukemias, is a promising new approach. Recently immunotherapies using T cells engineered to recognize DMG through Chimeric Antigen Receptors (CAR-T cells), successfully completed phase 1 trials. In these trials, CAR-T cells showed safety and striking effectiveness in individual patients. However, most DMG patients in these CAR-T trials suffered recurrence, suggesting that cure will likely require additional improvements to immunotherapy. To meet the need for improved immunotherapies, we propose to use gdT cells, which recognize and kill tumor cells even without CARs, to test new types of CAR-like innovations, and to add concurrent treatment with ResiPOx an immune stimulating agent that we formulated in nanoparticles to help it cross the blood brain barrier. We propose that these key innovations can bring about a step change and make immunotherapy for DMG newly effective.