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.
We propose to develop a novel, neurosurgical instrument that is minimally invasive and can rapidly and safely remove brain tumor tissue. Novel anti-cancer treatments can then be delivered into the cavity, where they can interact directly with the tumor. Successful development of this instrument will directly impact public health by providing alternative therapies for malignant tumors and potentially, blood clots in the brain.
|Brown, Christine E; Alizadeh, Darya; Starr, Renate et al. (2016) Regression of Glioblastoma after Chimeric Antigen Receptor T-Cell Therapy. N Engl J Med 375:2561-9|
|Ouyang, Mao; White, Ethan E; Ren, Hui et al. (2016) Metronomic Doses of Temozolomide Enhance the Efficacy of Carbon Nanotube CpG Immunotherapy in an Invasive Glioma Model. PLoS One 11:e0148139|
|Brown, Christine E; Badie, Behnam; Barish, Michael E et al. (2015) Bioactivity and Safety of IL13RÎ±2-Redirected Chimeric Antigen Receptor CD8+ T Cells in Patients with Recurrent Glioblastoma. Clin Cancer Res 21:4062-72|
|White, Ethan E; Pai, Alex; Weng, Yiming et al. (2015) Functionalized iron oxide nanoparticles for controlling the movement of immune cells. Nanoscale 7:7780-9|
|Chen, Xuebo; Zhang, Leying; Zhang, Ian Y et al. (2014) RAGE expression in tumor-associated macrophages promotes angiogenesis in glioma. Cancer Res 74:7285-97|