Developing a patient-derived B-cell-based vaccine, a novel therapeutic agent for glioblastomas

Glioblastomas (GBM) are characterized by their ability to create a strong immunosuppressive environment that blocks patient anti-tumor immune response. Dendritic cells are the typical antigen presenting cells, but DC-based therapies have not shown significant therapeutic effects against GBM so far, leading to research into other APCs to use for cell-based therapies. B cells are also known for their ability to take up, process, and present antigens for T-cell activation. The use of B cells as APCs for treating cancer has advantages over DC-based therapies (DCVax), including: I) more efficient tumor infiltration compared to DC; II) potential for generating tumor-reactive antibodies; and III) relative ease of rapid ex-vivo expansion of patient derived B cells, resulting in quicker and cheaper personalized treatments. Building on our expertise in brain tumor immunology and B-cell biology, we propose to generate an innovative immunotherapeutic approach by means of proinflammatory 4-1BBL expressing B cells as a source of potent B-cell-based vaccine (BVax) that will promote anti-GBM immune response. The proposed experiments will provide valuable mechanistic insights on how BVax can be utilized as an innovative anti-GBM immunotherapy.