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In recent years, the development and use of CAR-T cell therapy in hematological malignancies has shown great success. However, in solid tumors, this success has yet to be replicated. The solid tumor environment poses many challenges for cell-based therapies, due to factors such as high levels of immunosuppression, high levels of tumor heterogeneity, and difficulties with immune cell penetration and trafficking. In high-grade central nervous system (CNS) tumors, such as glioblastoma, these challenges are further exacerbated due to the presence of the blood-brain barrier. Current treatment modalities for these tumors are intense, and there is an urgent unmet clinical need for more effective, less toxic, tumor-specific treatment strategies. Immunotherapeutic approaches, and particularly CAR-based therapies, are known for possessing a more targeted nature than conventional treatment modalities, thus present a promising alternative approach in the treatment of pediatric brain tumors.
In this project, we aim to develop CAR-based therapies for application in these high-grade CNS tumors. We will explore the use of nanobody-based technology in a CAR targeting B7H3, a molecule which is highly expressed on the surface of glioblastoma cells. Furthermore, we will investigate the potential of different cellular sources, such as NK cells, for use in CAR-based therapies for high-grade CNS tumors, as alternative cell types may help circumvent some of the challenges presented by the solid tumor environment. Ultimately, we aim to provide new, effective, cell-based treatment options for use in high-grade CNS tumors.