IMMU-88. Expanding the Therapeutic Potential of Bvax: A B Cell Based Therapy for Brain Metastases and Immune-Excluded Solid Tumors

Abstract Glioblastoma (GBM) presents a major clinical challenge due to its highly invasive nature and resistance to treatment. We previously developed Bvax, a novel B cell based cancer therapy. In preclinical models of GBM, Bvax elicited robust antitumor immunity by enriching a subpopulation of CD8+ T cells characterized by high TCF-1 and low PD-1 expression. Additionally, Bvax differentiated into plasma cells that secreted antibodies targeting tumor-associated proteins involved in motility and matrix remodeling, potentially disrupting tumor progression and enhancing immune infiltration. A first-in-human (FIH) Phase I clinical trial at Northwestern University evaluates the safety and feasibility of Bvax in patients with newly diagnosed GBM. Given its dual mechanism and preclinical efficacy in GBM, we now expanded exploration of the therapeutic potential of Bvax into solid tumors such as lung and prostate cancer. The present study aims to characterize the effects of Bvax on tumor growth, survival, and the preferential migration and functionality of Bvax in these new models. We first demonstrated that weekly intravenous Bvax administration in prostate tumor bearing mice, beginning 21 days after tumor induction, led to measurable tumor regression. Tumor volume was monitored regularly, and animals were sacrificed at predefined tumor size thresholds to model survival. Additionally, in a lung tumor model, we leveraged CD45.1 and CD45.2 congenic mice to evaluate Bvax biodistribution and observed a marked increase in Bvax infiltration within the tumor, indicating strong tumor tropism. Given that primary lung tumors are a frequent source of brain metastases, these findings prompted us to explore Bvax in this treatment resistant setting. We aim to leverage Bvax’s antigen-presenting and antibody-secreting capabilities to intercept circulating tumor cells before they establish metastatic brain lesions, offering a novel therapeutic strategy for treating immune-excluded and hard-to-reach malignancies.