扩展Bvax的治疗潜力：一种基于B细胞的实体瘤疫苗

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 TCF1 and low PD-1 expression. Additionally, Bvax differentiated into plasma cells that secreted antibodies targeting tumor-associated proteins involved in motility and matrix remodeling, suggesting the disruption of tumor progression and enhanced 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 the encouraging preclinical results in GBM, we explored therapeutic potential of Bvax for other solid tumors, namely lung and prostate cancer. This study aims to characterize the effects of Bvax on tumor growth, survival, and the preferential migration of Bvax in these new models. To assess Bvax in a lung cancer model, we utilized an orthotopic KP (Kras/p53 mutated) lung tumor model that recapitulates KRAS-driven non-small cell lung cancer (NSCLC). Bvax treatment resulted in a marked survival extension (median 39 vs. 17 days) in tumor bearing mice compared to controls (Wilcoxon p = 0.046). To further assess biodistribution, we used B cell knockout (muMt) mice and observed enriched Bvax infiltration within the tumor, confirming strong tumor tropism within the lung microenvironment. We next evaluated Bvax in a subcutaneous prostate tumor model known for immune exclusion and poor immunotherapy responsiveness. Twenty one days after tumor induction, Bvax was administered and tumor volumes were measured regularly until they reached the defined size endpoint. At peak treatment response, tumor volumes were reduced by 68% relative to controls, accompanied by a higher percentage of MHC-II tumor-infiltrating B cells. These results suggest Bvax retains efficacy across several tumor types with restricted immune infiltration. Ongoing work is now evaluating Bvax in combination with standard-of-care regimens across both tumor models to determine whether its therapeutic activity can be enhanced. In parallel, we are performing immunophenotyping analyses to define how Bvax reshapes the immune landscape within the tumor and surrounding tissue, and better quantify Bvax infiltration across tumor compartments. Additionally, to support translational relevance, we are extending these investigations into patient-derived samples to assess Bvax function in human disease contexts.