Development of B-cell-based vaccine for Glioblastoma

/ABSTRACT 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 IFNγ 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. 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. Our preliminary data obtained under the parental 5R37CA258426 proposal showed that BVax promotes the expansion of clones that differ from CD8 T cells activated by dendritic cells (DC) and the proliferation of stem-like TCF-1+ CD8 T cells. In addition, we provided solid evidence that BVax produces antibodies that react to tumor-associated antigens and inhibit tumor growth. Our central hypothesis is that the BVax have unique properties as antigen-presenting and antibody- producing cells. More specifically, BVax might present a different set of antigens to CD8 T cells. In addition, BVax monoclonal antibodies (mAbs) might have a potential therapeutic effect. This research proposal aims to deep-dive into the immune mechanisms underlying this protection and prevention of tumor growth. We will focus on two processes: antigen presentation and activation of CD8+ T-cell memory formation (Aim 1) and the characterization (sequencing and cloning) of single-BVax monoclonal Ab production (Aim 2). Overall, our study provides a novel alternative to current immunotherapeutic approaches that can be readily translated to the clinic. Project Number: 4R37CA258426-06 | Fiscal Year: 2026 | NIH Institute/Center: National Cancer Institute (NCI) | Principal Investigator: Catalina Lee Chang | Institution: NORTHWESTERN UNIVERSITY, CHICAGO, IL | Award Amount: $362,482 | Activity Code: R37 View on NIH RePORTER: https://reporter.nih.gov/project-details/11129478