Novel Cell Delivery Method for Brain Tumor Therapy

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DESCRIPTION (provided by applicant): Even when treated with aggressively with current therapies, most patients with primary malignant brain tumors (glioma) survive less than two years. Although targeted therapies are being developed, the blood-brain barrier prevents large molecules from penetrating the central nervous system and moving to the brain. Because gliomas rarely metastasize, a localized tumor treatment could be sufficient to prevent the disease from progressing. As a result, methods are being developed to allow for the delivery of tumor-specific macromolecules directly into the brain tumors. However, these approaches require infusions of high-volumes of drugs which can be time consuming or impractical in an organ with limited space capacity, such as the brain. Thus, there is a pressing need for improved methods to deliver targeted macromolecules into brain tumors. The goal of this project is to fabricate and evaluate the feasibility of a novel instrument that is capable of creating a cavity within brain tumors using image-guided, minimally invasive techniques. The cavity that is generated by the instrument can then be used as a reservoir to deliver anti-cancer macromolecules or cells directly into the tumor. Using image guidance, the instrument is inserted into the tumor through a small burr hole for central tumor debulking. The unique mechanical features of this instrument will allow it to detach, fragment, cauterize and aspirate the tumor tissue through a small channel. Initial studies using proof-of concept prototypes have demonstrated the mechanical feasibility of this approach. Here, we propose to fabricate prototypes of a pre-clinical grade device, and characterize the performance of this instrument in vitro and in vivo. After completing this project, we expect to generate instrument designs for fabricating clinical- grade prototypes that are suitable for testing in human safety trials.