Immunotherapy has revolutionized the treatment of many tumors. However, most GBM patients have not, so far, benefited from immunotherapeutic treatment. With the goal of exploring ways to boost anti-GBM immunity, we've developed a B-cell-based vaccine (BVax) that consists of 4-1BBL+ B cells activated with CD40 agonism, BAFF and IFN? stimulation. BVax migrate to key secondary lymphoid organs and are proficient at antigen cross-presentation, which promotes both the survival and functionality of CD8+ T cells. A combination of radiation, BVax, and PD-L1 blockade conferred tumor eradication in 80% of treated tumor-bearing animals. This research proposal aims to understand the immune mechanisms underlying this protection and prevention of tumor growth. We will focus on two processes: generation of CD8+ T-cell memory formation (Aim 1) and Ab production (Aim 2). We hypothesize that both effector functions elicit protective anti-GBM immunity. We have been successful at generating GBM patient-derived BVax that activated autologous CD8+ T cells, which shows a strong ability to kill autologous glioma cells. This demonstrates that BVax can be produced from patient's peripheral blood. We now aim to further characterize and optimize BVax treatment protocol to inform future clinical application of this therapeutic approach (Aim 3). Overall, our study provides a novel alternative to current immunotherapeutic approaches that can be readily translated to the clinic.
Immunotherapy is a promising approach to treat glioblastoma patients, yet its efficacy so far has been very limited. Our work provides an opportunity to explore the B-cell-based vaccine as immunotherapy to treat deadly tumors, including glioblastoma. Our approach utilizes 4-1BBL+ B cells as a cellular platform to promote anti-tumor immunity.