Research And Grants

Monitoring Nanobody-Based B7H3 CAR-T Cell Behavior and Efficacy in Diffuse Midline Glioma

Diffuse intrinsic pontine glioma (DIPG) or midline glioma (DMG) are highly aggressive brain tumors and the leading cause of cancer related death in children. These tumors often cannot be surgically removed and to date, treatment with several types of chemotherapy has not been effective. As radiotherapy, the other cornerstone of cancer treatment, only temporarily alleviates symptoms without leading to cure, we need alternative forms of treatment, such as immunotherapy to increase survival. Here, we will study the potential of a specific type of immunotherapy, called CAR T-cell therapy that uses a patient's (genetically engineered) own (immune)-T cells to attack the tumor. Therefore, we have designed various CAR T-cells (CARs) with a special type of antibody fragment, called a nanobody, that targets B7H3, a protein at the surface of DMG cells. As nanobodies are smaller and more stable than traditional antibodies, nanobody-based CARs may have a better brain penetration than conventional CARs, leading to a higher effectivity and better tolerance. In this project, we will test the effectiveness of these nanobody-based CARs in DMG-animal models and use advanced imaging to track their behavior in the brain. These experiments may assist to develop safer and more effective treatments for children with DMG.