Grant: Project Grant

There is a great need for glioblastoma (GBM) treatments. Every year 3000 Canadians are diagnosed with brain or spinal cord cancer. GBM occurs at an incidence rate of 6.95 per 100,000 people over the age of 40. Patients face low survival rates (15-months median; 5% after 5 years). Immunotherapies offer great hope for new treatments but are hindered by the blood brain barrier, which impedes drug penetration, and anti-inflammatory environments that prevent efficacy with immunotherapies. We must develop drug delivery strategies that (1) promote and maintain efficacious drug concentrations in brain tumors, and (2) engineer the tumor from anti-inflammatory to "immune-active", where immune cells kill cancer cells. We propose to inject hydrogels that release immunotherapeutics directly into the tumor. The intracranial placement of hydrogels will dramatically improve drug accumulation in brain tumors compared to traditional intravenous administrations. Our lab has developed hydrogels that can sustain the release of immunotherapeutics after injection into tumors. To efficiently identify potential treatments, we will use 3D cellular models to study the influence of drug infusion rates on tumor environments and killing. We will control the release of two different drugs: (1) interleukin-12 (IL-12) to remodel the tumor environment from anti-inflammatory to "immune-active"; and (2) a bispecific T cell engager (BiTE) that redirect T cells, a type of immune cell, to kill tumors. We will then use our hydrogel delivery system in a GBM mouse model to quantify tumor killing. This research will demonstrate that hydrogels injected into GBM tumors improve the efficacy of cancer immunotherapeutics, patient quality of life and treatment accessibility. Our goal is to provide a treatment for GBM that dramatically improves patient survival and decreases cancer recurrence rates.