Glioblastoma Cell Lysate and Adjuvant Nanovaccines via Strategic Vaccination Completely Regress Established Murine Tumors

Abstract
Tumor vaccines have shown great promise for treating various malignancies; however, glioblastoma (GBM), characterized by its immunosuppressive tumor microenvironment, high heterogeneity, and limited accessibility, has achieved only modest clinical benefits. Here, it is reported that GBM cell lysate nanovaccines boosted with TLR9 agonist CpG ODN (GlioVac) via a strategic vaccination regimen achieve complete regression of malignant murine GBM tumors. Subcutaneous administration of GlioVac promotes uptake by cervical lymph nodes and antigen presentation cells, bolstering antigen cross-presentation and infiltration of GBM-specific CD8+ T cells into the tumor. Notably, a regimen involving two subcutaneous and three intravenous vaccinations not only activates systemic anti-GBM immunity but also further enhances the tumor infiltration of cytotoxic T lymphocytes, effectively reshaping the “cold” GBM tumor into a “hot” tumor. This approach led to a state of tumor-free survival in 5 out of 7 mice bearing the established GL261 GBM model with complete protection from tumor rechallenge. In an orthotopic hRas-GBM model induced by a lentiviral plasmid, GlioVac resulted in ≈100% complete tumor regression. These findings suggest that GlioVac provides a personalized therapeutic vaccine strategy for glioblastoma.